tailieunhanh - Báo cáo y học: "Defective response of CD4+ T cells to retinoic acid and TGFb in systemic lupus erythematosus"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Defective response of CD4+ T cells to retinoic acid and TGFb in systemic lupus erythematosus. | Sobel et al. Arthritis Research Therapy 2011 13 R106 http content 13 3 R106 RESEARCH ARTICLE Open Access Defective response of CD4 T cells to retinoic acid and TGFb in systemic lupus erythematosus Eric S Sobel1 Todd M Brusko2 Ed J Butfiloski1 Wei Hou3 Shiwu Li2 Carla M Cuda1 4 Ariana N Abid1 5 Westley H Reeves1 and Laurence Morel2 Abstract Introduction CD25 FOXP3 CD4 regulatory T cells Tregs are induced by transforming growth factor b TGFb and further expanded by retinoic acid RA . We have previously shown that this process was defective in T cells from lupus-prone mice expressing the novel isoform of the Pbxl gene Pbx1-d. This study tested the hypothesis that CD4 T cells from systemic lupus erythematosus SLE patients exhibited similar defects in Treg induction in response to TGFb and RA and that PBX1-d expression is associated with this defect. Methods Peripheral blood mononuclear cells PBMCs were collected from 142 SLE patients and 83 healthy controls HCs . The frequency of total memory and naive CD4 T cells was measured by flow cytometry on fresh cells. PBX1 isoform expression in purified CD4 T cells was determined by reverse transcription polymerase chain reaction RT-PCR . PBMCs were stimulated for three days with anti-CD3 and anti-CD28 in the presence or absence of TGFp and RA. The expression of CD25 and FOXP3 on CD4 T cells was then determined by flow cytometry. In vitro suppression assays were performed with sorted CD25 and CD25- FOXP3 T cells. CD4 T cell subsets or their expansion were compared between patients and HCs with two-tailed Mann-Whitney tests and correlations between the frequencies of two subsets were tested with Spearman tests. Results The percentage of CD25- FOXP3 CD4 CD25- Tregs T cells was greater in SLE patients than in HCs but these cells contrary to their matched CD25 counterparts did not show a suppressive activity. RA-expansion of TGFb-induced CD25 Tregs was significantly lower in SLE patients than in HCs although