BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk...BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.展开更多
Objective:To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8<sup>+</sup>CD28<sup>+</sup> cytotoxic T lymphocyte(CTL) responses.Methods:Cell...Objective:To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8<sup>+</sup>CD28<sup>+</sup> cytotoxic T lymphocyte(CTL) responses.Methods:Cell-sized Dynabeads? M-450 Epoxy beads coated with H-2K<sup>b</sup>:Ig-TRP2<sub>(</sub>1811<sub>1</sub>1K<sub> </sub>and anti-CD28 antibody were used as artificial antigen-presenting cells(aAPCs) lo induce melanoma-specific CD8*CD28’ CTL responses with the help of IL-2I and IL-I5.Dimer staining,proliferation,ELISPOT,and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.Results:Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8CD28' CTLs.Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- y under the slimulalion of H-2K:Ig-TRP2-aAPCs,TL-15,and IL-21.In addition,cytoloxicily experiments showed lhat induced CTLs have specific killing activity of target cells.Conclusions:The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8<sup>+</sup>CD28<sup>+</sup> CTLs against the melanoma.Our study provides evidence for a novel adoptive immunotherapy against tumors.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
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 inflammation.METHODS: Urothelium-ovalbumin(URO-OVA)/OTII mice, a double transgenic line that expresses the membrane f...AIM: To investigate the role of regulatory T(Treg) cells in CD4+ T cell-mediated bladder autoimmune inflammation.METHODS: Urothelium-ovalbumin(URO-OVA)/OTII 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 specific 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 inflammation. To facilitate Treg cell analysis, we further developed URO-OVAGFP-Foxp3/OT-II mice, a derived line of URO-OVA/OT-II mice that express the green fluorescent protein(GFP)-forkhead box protein P3(Foxp3) fusion protein. RESULTS: URO-OVA/OT-II mice failed to develop bladder inflammation despite the presence of autoreactive CD4+ T cells. By monitoring GFP-positive cells, bladder infiltration of CD4+ Treg cells was observed in URO-OVAGFP-Foxp3/OTII mice. The infiltrating Treg cells were functionally active and expressed Treg cell effector molecule as well as marker m RNAs including transforming growth factor-b, interleukin(IL)-10, fibrinogen-like protein 2, and glucocorticoid-induced tumor necrosis factor receptor(GITR). Studies further revealed that Treg cells from URO-OVAGFP-Foxp3/OT-II mice were suppressive and inhibited autoreactive CD4+ T cell proliferationand interferon(IFN)-g production in response to OVA Ag stimulation. Depletion of GITR-positive cells led to spontaneous development of bladder inflammation and expression of inflammatory factor m RNAs for IFN-g, IL-6, tumor necrosis factor-a and nerve growth factor in URO-OVAGFP-Foxp3/OT-II mice. CONCLUSION: Treg cells specific for bladder epithelial Ag play an important role in immunological homeostasis and the control of CD4+ T cell-mediated bladder autoimmune inflammation.展开更多
in mice transgenic for an autoantibody,self-reactive B cells have been shown to be eliminated upon interaction with membranebound self-antigens in the periphery as well as in the bone marrow, suggesting that both imma...in mice transgenic for an autoantibody,self-reactive B cells have been shown to be eliminated upon interaction with membranebound self-antigens in the periphery as well as in the bone marrow, suggesting that both immature and mature B cells are eliminated by multimerization of surface immunoglobulins(0Ig).Activation B cells by antigens may thus require a second signal that inhibits sIg-mediated apoptosis.Such a second signal is likely to be provided by T helper cells,because B-cell tolerance is more easily induced in the absence of T helper cells.To assess the molecular nature of the signal that inhibits sIg-mediated apoptosis,we used anti-IgM--induced apoptotic death of WEHI-231B lymphoma cells as a model system.Here we report that the signal for abrogating sIg-mediated apoptosis is generated by association of the CD401 molecule on T-cells with the CD40molecule on WEHI-231 cells.T-cells help through CD50 may thus determine whether B cells are eliminated or activated upon interaction with antigens.展开更多
The cell surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood (CB) were studied. The CD34 + cells freshly isolated from CB displayed ...The cell surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood (CB) were studied. The CD34 + cells freshly isolated from CB displayed low CD95 expression. The combinations of cytokines such as SCF+FL could up regulate the expression of CD95 in vitro culture and tumor necrosis factor α (TNF α) and interon γ (IFN γ) further increased the CD95 expression induced by positive cytokines. The functional status of CD95 mediated apoptosis were analyzed by incubation of CD34 +CB cells in the presence of anti CD95 monoclonal antibodies (McAbs). The effects of anti CD95 McAbs were measured by viable cell counting, flow cytometry, LTIC and CFU C assays. A decrease of viable cells, CFU C and LTIC numbers were observed in the presence of anti CD95 McAbs and TNF α or IFN γ. However, growth factor deprivation or the early acting cytokine such as SCF and FL cross linking to CD95 caused low apoptosis of CD34 + cells. The correlation of increased intracytoplasmic levels of bcl 2 and the presence of CD95 on fresh CB CD34 + cells suggested that bcl 2 might be involved in protecting against CD95 mediated apoptosis of CB CD34 + cells.展开更多
AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ sta...AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ stage C or D.METHODS: Formalin fixed and paraffin embedded materials of primary tumors and corresponding lymph node metastases resected from 56 patients with Dukes′ stage C or D of colorectal carcinoma were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44variant exon 6 (CD44v6).RESULTS: Thirty-one of 56 patients (55.4 %) expressed PCNA in the primary sites and 36 of 56 patients (64.3 %)expressed PCNA in the metastatic lymph nodes. A significant relation in PCNA expression was observed between the primary site and the metastatic lymph node (0.010<P<0.025).Forty-one of 56 patients (73.2 %) expressed CD44v6 in the primary site and 39 of 56 patients (69.6 %) expressed CD44v6 in the metastatic lymph node. There was also an significant relationship of CD44v6 between the primary site and the metastatic lymph node (0.005<P<0.010). No difference was observed between expression of CD44v6 and PCNA in the primary site (0.250<P<0.500).CONCLUSION: This study partially demonstrates that tumor cells in metastatic lymph node of colorectal carcinoma still possess cell proliferation activity and metastatic ability of tumor cells in primary site. There may be no association between cell proliferation activity and metastatic ability in colorectal carcinoma.展开更多
Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production th...Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4<sup>+</sup> CD8β<sup>-</sup> (CD4) and CD4<sup>-</sup> CD8β<sup>-</sup> [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19<sup>+</sup>CD27<sup>-</sup> (naïve) and CD19<sup>+</sup>CD27<sup>+</sup> (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.展开更多
Objective To investigate the role of peripheral lymphocytes Sialyl Lewis(x) (CD15s) antigen before and after kidney transplantation. Methods Flow cytometry technique was applied to examine the expression of peripheral...Objective To investigate the role of peripheral lymphocytes Sialyl Lewis(x) (CD15s) antigen before and after kidney transplantation. Methods Flow cytometry technique was applied to examine the expression of peripheral lymphoid cell surface CD15s antigen after renal transplantation, and to evaluate various therapeutic regimen. Results The statistic analysis results of peripheral lymphoid cell surface CD15s antigen expression level showed that there was significant difference among the patients with acute rejection, long-term dialysis and with normal renal function post-transplant; significant difference of CD15s expression level between group of rejection and infection; no significant difference of CD15s expression among the different groups treated by various therapeutic regimens. Conclusion The different therapeutic regimen has no influence to CD15s expression; Detection of peripheral lymphoid cell surface CD15s antigen expression periodically, intelligently make convenience to understand suitable status of immunosuppression.展开更多
基金Supported by Grant-in-Aid for research by the Kitasato University Medical Center,No.H26-008the JSPS KAKENHI,No.17K16578+3 种基金the JSPS KAKENHI,No.26670609Takeda Science FoundationKitasato University Research Grant for Young ResearchersGrant-in-Aid for research from the Kitasato University Medical Center,No.H25-0006
文摘BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.
基金supported,in part,by grants from the Program for New Century Excellent Talents in University(NECT-10-0098)the National Natural Scientific Foundation of China(Nos.81072161.81000769.81172139.and 81060183)+3 种基金Programs for Changjiang Scholars and Innovative Research Team in University(No. IRT1119)Innovative Research Team in Guangxi Natural Science Foundation (No.2011-18-5)Fund for Distinguished Young Scholars in Guangxi Natural Science Foundation(2012jjFA40005)Project of science and technology of Guangxi (1140003A-17)
文摘Objective:To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8<sup>+</sup>CD28<sup>+</sup> cytotoxic T lymphocyte(CTL) responses.Methods:Cell-sized Dynabeads? M-450 Epoxy beads coated with H-2K<sup>b</sup>:Ig-TRP2<sub>(</sub>1811<sub>1</sub>1K<sub> </sub>and anti-CD28 antibody were used as artificial antigen-presenting cells(aAPCs) lo induce melanoma-specific CD8*CD28’ CTL responses with the help of IL-2I and IL-I5.Dimer staining,proliferation,ELISPOT,and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.Results:Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8CD28' CTLs.Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- y under the slimulalion of H-2K:Ig-TRP2-aAPCs,TL-15,and IL-21.In addition,cytoloxicily experiments showed lhat induced CTLs have specific killing activity of target cells.Conclusions:The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8<sup>+</sup>CD28<sup>+</sup> CTLs against the melanoma.Our study provides evidence for a novel adoptive immunotherapy against tumors.
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 inflammation.METHODS: Urothelium-ovalbumin(URO-OVA)/OTII 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 specific 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 inflammation. To facilitate Treg cell analysis, we further developed URO-OVAGFP-Foxp3/OT-II mice, a derived line of URO-OVA/OT-II mice that express the green fluorescent protein(GFP)-forkhead box protein P3(Foxp3) fusion protein. RESULTS: URO-OVA/OT-II mice failed to develop bladder inflammation despite the presence of autoreactive CD4+ T cells. By monitoring GFP-positive cells, bladder infiltration of CD4+ Treg cells was observed in URO-OVAGFP-Foxp3/OTII mice. The infiltrating Treg cells were functionally active and expressed Treg cell effector molecule as well as marker m RNAs including transforming growth factor-b, interleukin(IL)-10, fibrinogen-like protein 2, and glucocorticoid-induced tumor necrosis factor receptor(GITR). Studies further revealed that Treg cells from URO-OVAGFP-Foxp3/OT-II mice were suppressive and inhibited autoreactive CD4+ T cell proliferationand interferon(IFN)-g production in response to OVA Ag stimulation. Depletion of GITR-positive cells led to spontaneous development of bladder inflammation and expression of inflammatory factor m RNAs for IFN-g, IL-6, tumor necrosis factor-a and nerve growth factor in URO-OVAGFP-Foxp3/OT-II mice. CONCLUSION: Treg cells specific for bladder epithelial Ag play an important role in immunological homeostasis and the control of CD4+ T cell-mediated bladder autoimmune inflammation.
文摘in mice transgenic for an autoantibody,self-reactive B cells have been shown to be eliminated upon interaction with membranebound self-antigens in the periphery as well as in the bone marrow, suggesting that both immature and mature B cells are eliminated by multimerization of surface immunoglobulins(0Ig).Activation B cells by antigens may thus require a second signal that inhibits sIg-mediated apoptosis.Such a second signal is likely to be provided by T helper cells,because B-cell tolerance is more easily induced in the absence of T helper cells.To assess the molecular nature of the signal that inhibits sIg-mediated apoptosis,we used anti-IgM--induced apoptotic death of WEHI-231B lymphoma cells as a model system.Here we report that the signal for abrogating sIg-mediated apoptosis is generated by association of the CD401 molecule on T-cells with the CD40molecule on WEHI-231 cells.T-cells help through CD50 may thus determine whether B cells are eliminated or activated upon interaction with antigens.
基金This project was supported by a grant from National Na-ture Science Foundation of China (No.3992 80 10 )
文摘The cell surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood (CB) were studied. The CD34 + cells freshly isolated from CB displayed low CD95 expression. The combinations of cytokines such as SCF+FL could up regulate the expression of CD95 in vitro culture and tumor necrosis factor α (TNF α) and interon γ (IFN γ) further increased the CD95 expression induced by positive cytokines. The functional status of CD95 mediated apoptosis were analyzed by incubation of CD34 +CB cells in the presence of anti CD95 monoclonal antibodies (McAbs). The effects of anti CD95 McAbs were measured by viable cell counting, flow cytometry, LTIC and CFU C assays. A decrease of viable cells, CFU C and LTIC numbers were observed in the presence of anti CD95 McAbs and TNF α or IFN γ. However, growth factor deprivation or the early acting cytokine such as SCF and FL cross linking to CD95 caused low apoptosis of CD34 + cells. The correlation of increased intracytoplasmic levels of bcl 2 and the presence of CD95 on fresh CB CD34 + cells suggested that bcl 2 might be involved in protecting against CD95 mediated apoptosis of CB CD34 + cells.
文摘AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ stage C or D.METHODS: Formalin fixed and paraffin embedded materials of primary tumors and corresponding lymph node metastases resected from 56 patients with Dukes′ stage C or D of colorectal carcinoma were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44variant exon 6 (CD44v6).RESULTS: Thirty-one of 56 patients (55.4 %) expressed PCNA in the primary sites and 36 of 56 patients (64.3 %)expressed PCNA in the metastatic lymph nodes. A significant relation in PCNA expression was observed between the primary site and the metastatic lymph node (0.010<P<0.025).Forty-one of 56 patients (73.2 %) expressed CD44v6 in the primary site and 39 of 56 patients (69.6 %) expressed CD44v6 in the metastatic lymph node. There was also an significant relationship of CD44v6 between the primary site and the metastatic lymph node (0.005<P<0.010). No difference was observed between expression of CD44v6 and PCNA in the primary site (0.250<P<0.500).CONCLUSION: This study partially demonstrates that tumor cells in metastatic lymph node of colorectal carcinoma still possess cell proliferation activity and metastatic ability of tumor cells in primary site. There may be no association between cell proliferation activity and metastatic ability in colorectal carcinoma.
文摘Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4<sup>+</sup> CD8β<sup>-</sup> (CD4) and CD4<sup>-</sup> CD8β<sup>-</sup> [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19<sup>+</sup>CD27<sup>-</sup> (naïve) and CD19<sup>+</sup>CD27<sup>+</sup> (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.
基金This work was supported by the Xi'an Jiaotong University Doctor Fund (No.y100.011005)
文摘Objective To investigate the role of peripheral lymphocytes Sialyl Lewis(x) (CD15s) antigen before and after kidney transplantation. Methods Flow cytometry technique was applied to examine the expression of peripheral lymphoid cell surface CD15s antigen after renal transplantation, and to evaluate various therapeutic regimen. Results The statistic analysis results of peripheral lymphoid cell surface CD15s antigen expression level showed that there was significant difference among the patients with acute rejection, long-term dialysis and with normal renal function post-transplant; significant difference of CD15s expression level between group of rejection and infection; no significant difference of CD15s expression among the different groups treated by various therapeutic regimens. Conclusion The different therapeutic regimen has no influence to CD15s expression; Detection of peripheral lymphoid cell surface CD15s antigen expression periodically, intelligently make convenience to understand suitable status of immunosuppression.