Enteropathy-associated T-cell lymphoma （EATL） is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac dis...Enteropathy-associated T-cell lymphoma （EATL） is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac disease, in which cells are characterized by being monomorphic and small- to medium-sized. Cells are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain. We present an atypical case of type 2 EATL in the jejunum, with human T-lymphotropic virus-1 that was CD4- CDS＋ CD56- CD30- CD25- TIA-I＋ and granzyme B＋ on immunohistological staining. It also displayed translocation of chromosome 8p24 （c-MYC）, as de- termined by fluorescent/n situ hybridization. Mucosalspreading and intraepithelial invasion by lymphoma with villous atrophy were detected adjacent to the mucosal layer. The lymphoma may be derived from in- traepithelial CD8＋ T cells, similar to celiac disease.展开更多
Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total ...Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4^+ and CD8^+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed. Results The clone burden of MDS patients was 67.4%±36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14.28 g/L and 76.40±24.44 g/L, (1.82±0.48)×10~ 12 /L and (2.32±0.66)×10~ 12 /L, respectively (all P<0.05). CD4^+ T lymphocytes of MDS patients and normal controls were (0.274±0.719)×10~ 9 /L and (0.455±0.206)×10~ 9 /L, respectively (P<0.05). CD8^+ T lymphocytes of MDS patients and normal controls were (0.240±0.150)×10~ 9 /L and (0.305±0.145)×10~ 9 /L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40 ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90±0.52) than that in low clone burden patients (0.97±0.44, P<0.05). Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.展开更多
AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis model.METHODS:The trinitrobenzene sulfonate(TNBS) model of induced colitis was use...AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis model.METHODS:The trinitrobenzene sulfonate(TNBS) model of induced colitis was used in Balb/c mice.Subsequently after intravenous adeno-associated virusmediated regulatory T-cell epitopes(Tregitope) delivery,acute colitis was initiated by intra-rectal administration of 1.5 mg TNBS in 40% ethanol followed by a second treatment with TNBS(0.75 mg in 20% ethanol) 8 d later.Control groups included mice not treated with TNBS(healthy control group) and mice treated by TNBS only(diseased group).At the time of sacrifice colon weight,the disease activity index and histology damage score were determined.Immunohistochemical staining of the colonic tissues was performed to asses the cellular infiltrate and the presence of transcription factor forkhead Box-P3(Foxp3).Thymus,mesenteric lymph nodes,liver and spleen tissue were collected and the corresponding lymphocyte populations were further assessed by flow cytometry analysis for the expression of CD4+ T cell and regulatory T cell associated markers.RESULTS:The Tregitope 167 treated mice gained an average of 4% over their initial body weight at the time of sacrifice.In contrast,the mice treated with TNBS alone(no Tregitope) developed colitis,and lost 4% of their initial body weight at the time of sacrifice(P < 0.01).The body weight increase that had been observed in the mice pre-treated with Tregitope 167 was substantiated by a lower disease activity index and a decreased colon weight as compared to the diseased control group(P < 0.01 and P < 0.001,respectively).Immunohistochemical staining of the colonic tissues for CD4+ showed that inflammatory cell infiltrates were present in TNBS treated mice with or without administration with tregitope 167 and that these cellular infiltrates consisted mainly of CD4+ cells.For both TNBS treated groups CD4+ T cell infiltrates were observed in the sub-epithelial layer and the lamina propria.CD4+ T cell infiltrates were also present in the muscularis mucosa layer of the diseased control mice,but were absent in the Tregitope 167 treated group.Numerous Foxp3 positive cells were detected in the lamina propria and sub-epithelium of the colon sections from mice treated with Tregitope 167.Furthermore,the Foxp3 and glycoprotein A repetitions predominant markers were significantly increased in the CD4+ T lymphocyte population in the thymus of the mice pre-treated with adeno-associated virus serotype 5(cytomegalovirus promoter-Tregitope 167),as cytomegalovirus promoter compared to lymphocyte populations in the thymus of diseased and the healthy control mice(P < 0.05 and P < 0.001,respectively).CONCLUSION:This study identifies adeno-associated virus-mediated delivery of regulatory T-cell epitope 167 as a novel anti-inflammatory approach with the capacity to decrease intestinal inflammation and induce longterm remission in inflammatory bowel disease.展开更多
文摘Enteropathy-associated T-cell lymphoma （EATL） is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac disease, in which cells are characterized by being monomorphic and small- to medium-sized. Cells are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain. We present an atypical case of type 2 EATL in the jejunum, with human T-lymphotropic virus-1 that was CD4- CDS＋ CD56- CD30- CD25- TIA-I＋ and granzyme B＋ on immunohistological staining. It also displayed translocation of chromosome 8p24 （c-MYC）, as de- termined by fluorescent/n situ hybridization. Mucosalspreading and intraepithelial invasion by lymphoma with villous atrophy were detected adjacent to the mucosal layer. The lymphoma may be derived from in- traepithelial CD8＋ T cells, similar to celiac disease.
基金Supported by a grant from the Tianjin Natural Science Fund (013111111,023609311).
文摘Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4^+ and CD8^+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed. Results The clone burden of MDS patients was 67.4%±36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14.28 g/L and 76.40±24.44 g/L, (1.82±0.48)×10~ 12 /L and (2.32±0.66)×10~ 12 /L, respectively (all P<0.05). CD4^+ T lymphocytes of MDS patients and normal controls were (0.274±0.719)×10~ 9 /L and (0.455±0.206)×10~ 9 /L, respectively (P<0.05). CD8^+ T lymphocytes of MDS patients and normal controls were (0.240±0.150)×10~ 9 /L and (0.305±0.145)×10~ 9 /L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40 ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90±0.52) than that in low clone burden patients (0.97±0.44, P<0.05). Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.
基金Supported by Grant from the Broad Medical Research Program of The Broad Foundation,No. IBD-029 5R
文摘AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis model.METHODS:The trinitrobenzene sulfonate(TNBS) model of induced colitis was used in Balb/c mice.Subsequently after intravenous adeno-associated virusmediated regulatory T-cell epitopes(Tregitope) delivery,acute colitis was initiated by intra-rectal administration of 1.5 mg TNBS in 40% ethanol followed by a second treatment with TNBS(0.75 mg in 20% ethanol) 8 d later.Control groups included mice not treated with TNBS(healthy control group) and mice treated by TNBS only(diseased group).At the time of sacrifice colon weight,the disease activity index and histology damage score were determined.Immunohistochemical staining of the colonic tissues was performed to asses the cellular infiltrate and the presence of transcription factor forkhead Box-P3(Foxp3).Thymus,mesenteric lymph nodes,liver and spleen tissue were collected and the corresponding lymphocyte populations were further assessed by flow cytometry analysis for the expression of CD4+ T cell and regulatory T cell associated markers.RESULTS:The Tregitope 167 treated mice gained an average of 4% over their initial body weight at the time of sacrifice.In contrast,the mice treated with TNBS alone(no Tregitope) developed colitis,and lost 4% of their initial body weight at the time of sacrifice(P < 0.01).The body weight increase that had been observed in the mice pre-treated with Tregitope 167 was substantiated by a lower disease activity index and a decreased colon weight as compared to the diseased control group(P < 0.01 and P < 0.001,respectively).Immunohistochemical staining of the colonic tissues for CD4+ showed that inflammatory cell infiltrates were present in TNBS treated mice with or without administration with tregitope 167 and that these cellular infiltrates consisted mainly of CD4+ cells.For both TNBS treated groups CD4+ T cell infiltrates were observed in the sub-epithelial layer and the lamina propria.CD4+ T cell infiltrates were also present in the muscularis mucosa layer of the diseased control mice,but were absent in the Tregitope 167 treated group.Numerous Foxp3 positive cells were detected in the lamina propria and sub-epithelium of the colon sections from mice treated with Tregitope 167.Furthermore,the Foxp3 and glycoprotein A repetitions predominant markers were significantly increased in the CD4+ T lymphocyte population in the thymus of the mice pre-treated with adeno-associated virus serotype 5(cytomegalovirus promoter-Tregitope 167),as cytomegalovirus promoter compared to lymphocyte populations in the thymus of diseased and the healthy control mice(P < 0.05 and P < 0.001,respectively).CONCLUSION:This study identifies adeno-associated virus-mediated delivery of regulatory T-cell epitope 167 as a novel anti-inflammatory approach with the capacity to decrease intestinal inflammation and induce longterm remission in inflammatory bowel disease.
