AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cel...AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cell line(Raw 264.7),mouse primary antigen-presenting cells(APCs,MHCII+) and CD11c+dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively.To confirm the anti-inflammatory effects of cinnamon extract in vivo,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression prof iles in inflamed tissue.RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells(DCs) by suppressing expression of co-stimulatory molecules(B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase(COX)-2.Cinnamon extract induced regulatory DCs(rDCs) that produce low levels of pro-inflammatory cytokines [interleukin(IL)-1β,IL-6,IL-12,interferon(IFN)-γ and tumor necrosis factor(TNF)-α] while expressing high levels of immunoregulatory cytokines(IL-10 and transforming growth factor-β).In addition,rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines(IL-1β,IFN-γ and TNF-α),while enhancing IL-10 levels.CONCLUSION:Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.展开更多
The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievem...The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved （including an estimate of the number of leucocyte surface molecules still to be discovered）, and how the field can best move forward.展开更多
Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism c...Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism causing transient infections. Despite all scientific efforts, there are still some gaps in the knowledge of the pathogenesis of this disease. Antigen presenting cells(APCs), as initiators of the immune response, are located in the first line of defense against microorganisms, and are responsible for antigen recognition, processing and presentation. Dendritic cells(DCs) are the main type of APC involved in antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV replication in DCs may trigger off different mechanisms to impair the onset of a host effective immune response against the virus. On the one side, PRRSV may impair the basic functions of DCs by regulating the expression of major histocompatibility complex class Ⅱ and CD80/86. Other strategy followed by the virus is the induction of cell death of APCs by apoptosis, necrosis or both of them. The impairment and/or cell death ofAPCs could lead to a failure in the onset of an efficient immune response, as long as cells could not properly activate T cells. Future aspects to take into account are also discussed in this review.展开更多
Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus ha...Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.展开更多
INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SL...INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .展开更多
Fourier transform infrared spectroscopy(FTIR) and circular dichroism(CD) were used to investigate the conformational changes of heated whey protein(WP) and the corresponding changes in the hydrolysates immunoreactivit...Fourier transform infrared spectroscopy(FTIR) and circular dichroism(CD) were used to investigate the conformational changes of heated whey protein(WP) and the corresponding changes in the hydrolysates immunoreactivity were determined by competitive enzyme-linked immunosorbent assay(ELISA).Results showed that the contents of α-helix and β-sheet of WP did not decrease much under mild heating conditions and the antigenicity was relatively high;when the heating intensity increased(70 ℃ for 25 min or 75 ℃ for 20 min),the content of α-helix and β-sheet decreased to the minimum,so was the antigenicity;However,when the WP was heated at even higher temperature and for a longer time,the β-sheet associated with protein aggregation begun to increase and the antigenicity increased correspondingly.It was concluded that the conformations of heated WP and the antigenicity of its hydrolysates are related and the optimum structure for decreasing the hydrolysates antigeniity is the least content of α-helix and β-sheet.Establishing the relationship between the WP secondary structure and WP hydrolysates antigenicity is significant to supply the reference for antigenicity reduction by enzymolysis.展开更多
Objective:To investigate the prevalence of microbial antigenic components of circulating immune complexes amongst grades of CD4 T lymphocyte counts in HIV sero positive and seronegative participants.Methods:Polyethele...Objective:To investigate the prevalence of microbial antigenic components of circulating immune complexes amongst grades of CD4 T lymphocyte counts in HIV sero positive and seronegative participants.Methods:Polyethelene glycol(PEG-600) and buffering methods of precipitation and dissociation of immune complexes was used to generate immune solution from sera of 100 HIV sero-positive and 100 HIV sero-negative participants.These were categorized into 3 grades based on CD4 count:】 500 cell/mm,200-499 cell/mm3 and 【200 cell/mm3.The immune solutions were assayed using membrane based immunoassay and antibody titration, along side its unprocessed serum for detection of various microbial antigens and or antibodies. CD4 T cell counts were estimated using Patec Cyflow SL-3 Germany.Results:Antigenic component of immune complexes of various infectious agents was detected in 99 and 70 HIV seropositive and HIV sero-negative participants,respectively.In group A,there were 10 HIV positive participants,including 4(40.0%) had circulating immune complexes(CICs) due to Salmonella species only:1(10.0%) due to Salmonella-Plasmodium falciparum(P.falciparum),SalmonellaP. falciparum-HCV and P.falciparum antigens,respectively.In group B,45(45.4%) HIV seropositive participants with CICs had CD4 T lymphocyte count between 200-499 cells/mm^3.Out of these,20(44.4%) had CICs due to Salmonella species only:9(20%) due to Salmonella-P. falciparum.In group C,there were 44(44.4%) HIV sero-positive participants,including 3(6.8%) due to Salmonella species only:24(54.4%) due to Salmonella-P.falciparum:2(4.5%) due to P. falciparum only.Conclusions:In HIV sero-positive participants,presence of heterogeneity of Salmonella species-P.falciparum antigens was highly incriminated in CD4 count depletion but not homogeneity of malaria parasites antigens.Malaria parasites antigens only were incriminated in CD4^+ count depletion amongst HIV sero-negative participants.Before taking any decision on the management of HIV-1-positive individuals,their malaria and Salmonella paratyphi status should be assessed,but not malaria status alone.展开更多
Parasite-specific CD8+ T cells have been shown to transfer protection against nLeishmania major in susceptible BALB/c mice.An epitope-tagged expression library was used to identify the antigen recognized by a protecti...Parasite-specific CD8+ T cells have been shown to transfer protection against nLeishmania major in susceptible BALB/c mice.An epitope-tagged expression library was used to identify the antigen recognized by a protective CD8+ T cells clone. The expression library allowed recombinant proteins made in bacteria to be captured by macrophages for presentation to T cells restricted to major histompatibility complex class n. A conserved 36-kilodalton member of the tryptophanaspartic acid repeat family of proteins was identified that was expressed in both stages of the parasite life cycle. A 24-kilodalton portion of this antigen protected susceptible mice when administered as a vaccine with interleukin-12before injection.展开更多
T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for imm...T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.展开更多
AIM： To investigate the role of regulatory T （Treg） cells in CD4^＋ T cell-mediated bladder autoimmune infammation. METHODS： Urothelium-ovalbumin （URO-OVA）/OT-II mice, a double transgenic line that expresses the...AIM： To investigate the role of regulatory T （Treg） cells in CD4^＋ T cell-mediated bladder autoimmune infammation. METHODS： Urothelium-ovalbumin （URO-OVA）/OT-II mice, a double transgenic line that expresses the membrane form of the model antigen （Ag） OVA as a self-Ag on the urothelium and the OVA-specific CD4^＋ T cell receptor specifc for the I-Ab/OVA323-339 epitope in the periphery, were developed to provide an autoimmune environment for investigation of the role of Treg cells in bladder autoimmune infammation. To facilitate Treg cell analysis, we further developed URO-OVA^GFP-Foxp3/OT-II mice, a derived line of URO-OVA/OT-II mice that express the green fuorescent protein （GFP）-forkhead box protein P3 （Foxp3） fusion protein. RESULTS： URO-OVA/OT-II mice failed to develop bladder infammation despite the presence of autoreactive CD4^＋ T cells. By monitoring GFP-positive cells, bladder infltration of CD4^＋ Treg cells was observed in URO-OVA^GFP-Foxp3/OT-II mice. The infiltrating Treg cells were functionally active and expressed Treg cell effector molecule as well as marker mRNAs including transforming growth factor-β, interleukin （IL）-10, fibrinogen-like protein 2, and glucocorticoid-induced tumor necrosis factor receptor （GITR）. Studies further revealed that Treg cells from URO-OVA^GFP-Foxp3/OT-II mice were suppressive and inhibited autoreactive CD4^＋ T cell proliferation and interferon （IFN）-g production in response to OVA Ag stimulation. Depletion of GITR-positive cells led to spontaneous development of bladder infammation and expression of inflammatory factor mRNAs for IFN-γ, IL-6, tumor necrosis factor-α and nerve growth factor in URO-OVA^GFP-Foxp3/OT-II mice. CONCLUSION： Treg cells specifc for bladder epithelial Ag play an important role in immunological homeostasis and the control of CD4^＋ T cell-mediated bladder autoimmune infammation.展开更多
OBJECTIVE: To examine 10 cases with primary cutaneous CD30-positive anaplastic large cell lymphoma (ALCL), analyze their clinical manifestations and pathological and immunohistochemical features, and improve early dia...OBJECTIVE: To examine 10 cases with primary cutaneous CD30-positive anaplastic large cell lymphoma (ALCL), analyze their clinical manifestations and pathological and immunohistochemical features, and improve early diagnosis of this disease. METHODS: We studied the morphological characteristics of primary cutaneous CD30-positive ALCL using histopathological methods. Leukocyte common antigen (LCA), CD20, CD30, CD45RO, CD68, epithelial membrane antigen (EMA), cytokeratin (CK) and HMB45 antibodies were used to determine the expression of their respective antigens from routine paraffin samples of the patients. RESULTS: Ten patients (7 men and 3 women, aged 31 to 84 years) complained of subcutaneous masses or papular eruptions over their lower trunks and extremities. Histopathologically, the lesions were composed of numerous large round or oval pleomorphic cells. The cytoplasm was usually abundant, amphophilic or basophilic, and finely vacuolated. Nuclei were commonly eccentrically localized and lobated or horseshoed in shape, and multinucleated giant cells and Reed-Sternberg-like cells were seen. Nucleoli were generally multiple and large. Of the 10 patients, tumor cells displayed positive antigen expression of CD30 in all cases, positive CD45RO in 6 cases, positive CD20 in only 1 case, but negative CD45RO and CD20 expressions in 3 cases. Two patients died at 7 weeks and 3.4 years of follow-up, respectively. CONCLUSION: Our study highlights the importance of histopathologic features and positive CD30 staining for differentiation of this disease from other malignant skin tumors.展开更多
基金Supported by Grants from the BioGreen 21 Program, Rural Development Administration (PJ007054)Regional Technology Innovation Program of the MOCIE (RTI05-01-01)Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (A080588-20)
文摘AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cell line(Raw 264.7),mouse primary antigen-presenting cells(APCs,MHCII+) and CD11c+dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively.To confirm the anti-inflammatory effects of cinnamon extract in vivo,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression prof iles in inflamed tissue.RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells(DCs) by suppressing expression of co-stimulatory molecules(B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase(COX)-2.Cinnamon extract induced regulatory DCs(rDCs) that produce low levels of pro-inflammatory cytokines [interleukin(IL)-1β,IL-6,IL-12,interferon(IFN)-γ and tumor necrosis factor(TNF)-α] while expressing high levels of immunoregulatory cytokines(IL-10 and transforming growth factor-β).In addition,rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines(IL-1β,IFN-γ and TNF-α),while enhancing IL-10 levels.CONCLUSION:Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.
文摘The 8^th International Workshop on Human Leucocyte Differentiation Antigens （chaired by HZ and managed by BS） was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved （including an estimate of the number of leucocyte surface molecules still to be discovered）, and how the field can best move forward.
基金Supported by The Spanish Ministry of Education and Science,No.AGL2009-12438/GAN
文摘Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism causing transient infections. Despite all scientific efforts, there are still some gaps in the knowledge of the pathogenesis of this disease. Antigen presenting cells(APCs), as initiators of the immune response, are located in the first line of defense against microorganisms, and are responsible for antigen recognition, processing and presentation. Dendritic cells(DCs) are the main type of APC involved in antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV replication in DCs may trigger off different mechanisms to impair the onset of a host effective immune response against the virus. On the one side, PRRSV may impair the basic functions of DCs by regulating the expression of major histocompatibility complex class Ⅱ and CD80/86. Other strategy followed by the virus is the induction of cell death of APCs by apoptosis, necrosis or both of them. The impairment and/or cell death ofAPCs could lead to a failure in the onset of an efficient immune response, as long as cells could not properly activate T cells. Future aspects to take into account are also discussed in this review.
文摘Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.
文摘INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .
基金National Science and Technology Support Program(2009BADB9B06)Beijing Science and Technology Program(D10110504601002)
文摘Fourier transform infrared spectroscopy(FTIR) and circular dichroism(CD) were used to investigate the conformational changes of heated whey protein(WP) and the corresponding changes in the hydrolysates immunoreactivity were determined by competitive enzyme-linked immunosorbent assay(ELISA).Results showed that the contents of α-helix and β-sheet of WP did not decrease much under mild heating conditions and the antigenicity was relatively high;when the heating intensity increased(70 ℃ for 25 min or 75 ℃ for 20 min),the content of α-helix and β-sheet decreased to the minimum,so was the antigenicity;However,when the WP was heated at even higher temperature and for a longer time,the β-sheet associated with protein aggregation begun to increase and the antigenicity increased correspondingly.It was concluded that the conformations of heated WP and the antigenicity of its hydrolysates are related and the optimum structure for decreasing the hydrolysates antigeniity is the least content of α-helix and β-sheet.Establishing the relationship between the WP secondary structure and WP hydrolysates antigenicity is significant to supply the reference for antigenicity reduction by enzymolysis.
文摘Objective:To investigate the prevalence of microbial antigenic components of circulating immune complexes amongst grades of CD4 T lymphocyte counts in HIV sero positive and seronegative participants.Methods:Polyethelene glycol(PEG-600) and buffering methods of precipitation and dissociation of immune complexes was used to generate immune solution from sera of 100 HIV sero-positive and 100 HIV sero-negative participants.These were categorized into 3 grades based on CD4 count:】 500 cell/mm,200-499 cell/mm3 and 【200 cell/mm3.The immune solutions were assayed using membrane based immunoassay and antibody titration, along side its unprocessed serum for detection of various microbial antigens and or antibodies. CD4 T cell counts were estimated using Patec Cyflow SL-3 Germany.Results:Antigenic component of immune complexes of various infectious agents was detected in 99 and 70 HIV seropositive and HIV sero-negative participants,respectively.In group A,there were 10 HIV positive participants,including 4(40.0%) had circulating immune complexes(CICs) due to Salmonella species only:1(10.0%) due to Salmonella-Plasmodium falciparum(P.falciparum),SalmonellaP. falciparum-HCV and P.falciparum antigens,respectively.In group B,45(45.4%) HIV seropositive participants with CICs had CD4 T lymphocyte count between 200-499 cells/mm^3.Out of these,20(44.4%) had CICs due to Salmonella species only:9(20%) due to Salmonella-P. falciparum.In group C,there were 44(44.4%) HIV sero-positive participants,including 3(6.8%) due to Salmonella species only:24(54.4%) due to Salmonella-P.falciparum:2(4.5%) due to P. falciparum only.Conclusions:In HIV sero-positive participants,presence of heterogeneity of Salmonella species-P.falciparum antigens was highly incriminated in CD4 count depletion but not homogeneity of malaria parasites antigens.Malaria parasites antigens only were incriminated in CD4^+ count depletion amongst HIV sero-negative participants.Before taking any decision on the management of HIV-1-positive individuals,their malaria and Salmonella paratyphi status should be assessed,but not malaria status alone.
文摘Parasite-specific CD8+ T cells have been shown to transfer protection against nLeishmania major in susceptible BALB/c mice.An epitope-tagged expression library was used to identify the antigen recognized by a protective CD8+ T cells clone. The expression library allowed recombinant proteins made in bacteria to be captured by macrophages for presentation to T cells restricted to major histompatibility complex class n. A conserved 36-kilodalton member of the tryptophanaspartic acid repeat family of proteins was identified that was expressed in both stages of the parasite life cycle. A 24-kilodalton portion of this antigen protected susceptible mice when administered as a vaccine with interleukin-12before injection.
文摘T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.
基金Supported by The National Institutes of Health to Luo Y,No.RO1DK066079
文摘AIM： To investigate the role of regulatory T （Treg） cells in CD4^＋ T cell-mediated bladder autoimmune infammation. METHODS： Urothelium-ovalbumin （URO-OVA）/OT-II mice, a double transgenic line that expresses the membrane form of the model antigen （Ag） OVA as a self-Ag on the urothelium and the OVA-specific CD4^＋ T cell receptor specifc for the I-Ab/OVA323-339 epitope in the periphery, were developed to provide an autoimmune environment for investigation of the role of Treg cells in bladder autoimmune infammation. To facilitate Treg cell analysis, we further developed URO-OVA^GFP-Foxp3/OT-II mice, a derived line of URO-OVA/OT-II mice that express the green fuorescent protein （GFP）-forkhead box protein P3 （Foxp3） fusion protein. RESULTS： URO-OVA/OT-II mice failed to develop bladder infammation despite the presence of autoreactive CD4^＋ T cells. By monitoring GFP-positive cells, bladder infltration of CD4^＋ Treg cells was observed in URO-OVA^GFP-Foxp3/OT-II mice. The infiltrating Treg cells were functionally active and expressed Treg cell effector molecule as well as marker mRNAs including transforming growth factor-β, interleukin （IL）-10, fibrinogen-like protein 2, and glucocorticoid-induced tumor necrosis factor receptor （GITR）. Studies further revealed that Treg cells from URO-OVA^GFP-Foxp3/OT-II mice were suppressive and inhibited autoreactive CD4^＋ T cell proliferation and interferon （IFN）-g production in response to OVA Ag stimulation. Depletion of GITR-positive cells led to spontaneous development of bladder infammation and expression of inflammatory factor mRNAs for IFN-γ, IL-6, tumor necrosis factor-α and nerve growth factor in URO-OVA^GFP-Foxp3/OT-II mice. CONCLUSION： Treg cells specifc for bladder epithelial Ag play an important role in immunological homeostasis and the control of CD4^＋ T cell-mediated bladder autoimmune infammation.
文摘OBJECTIVE: To examine 10 cases with primary cutaneous CD30-positive anaplastic large cell lymphoma (ALCL), analyze their clinical manifestations and pathological and immunohistochemical features, and improve early diagnosis of this disease. METHODS: We studied the morphological characteristics of primary cutaneous CD30-positive ALCL using histopathological methods. Leukocyte common antigen (LCA), CD20, CD30, CD45RO, CD68, epithelial membrane antigen (EMA), cytokeratin (CK) and HMB45 antibodies were used to determine the expression of their respective antigens from routine paraffin samples of the patients. RESULTS: Ten patients (7 men and 3 women, aged 31 to 84 years) complained of subcutaneous masses or papular eruptions over their lower trunks and extremities. Histopathologically, the lesions were composed of numerous large round or oval pleomorphic cells. The cytoplasm was usually abundant, amphophilic or basophilic, and finely vacuolated. Nuclei were commonly eccentrically localized and lobated or horseshoed in shape, and multinucleated giant cells and Reed-Sternberg-like cells were seen. Nucleoli were generally multiple and large. Of the 10 patients, tumor cells displayed positive antigen expression of CD30 in all cases, positive CD45RO in 6 cases, positive CD20 in only 1 case, but negative CD45RO and CD20 expressions in 3 cases. Two patients died at 7 weeks and 3.4 years of follow-up, respectively. CONCLUSION: Our study highlights the importance of histopathologic features and positive CD30 staining for differentiation of this disease from other malignant skin tumors.
