title: APC dysfunction is correlated with defective suppression of T cell proliferation in human type 1 diabetes.
abstract: It is widely believed that CD4(+)CD25(+) regulatory T cells (Treg) are defective in type 1 diabetes (T1D) and other autoimmune diseases. However, this conclusion is based on the suboptimal in vitro suppression results from very small numbers of subjects. Furthermore, the cells responsible for the suboptimal suppression have not been defined. Therefore, we carried out extensive in vitro suppression assays using both autologous and heterologous donors of Tregs, effector T cells and antigen-presenting cells (APC) from both T1D patients and normal controls. Our in vitro suppression data indicated that a significantly higher proportion (40.0%) of T1D patients have "very low suppression" activity (defined as<25%) by autologous Treg compared to controls (6.3%) (p=0.002). Meta-analysis of the published results confirmed this observation with 45.7% low suppressors in T1D and 7.8% in controls (p=0.00002). Interestingly, suppression assays using heterologous Tregs, effector T cells and APC suggest that the source of APC is correlated with the suppression activity. The frequencies of CD4(+)CD25(+) and CD4(+)CD25(hi) T cells were found to increase with age in normal controls but not in T1D patients, resulting in significantly higher frequencies of CD4(+)CD25(+) (p=0.001) and CD4(+)CD25(hi) (p=0.009) T cells in young T1D subjects than age-matched controls but slightly lower CD4(+)CD25(+) (p=0.003) and CD4(+)CD25(hi) (p=0.08) T cells in old T1D subjects than age-matched controls.
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Jin
authors.forename: Xueqin
authors.initials: X
authors.lastname: Chen
authors.forename: Robert
authors.initials: R
authors.lastname: Podolsky
authors.forename: Diane
authors.initials: D
authors.lastname: Hopkins
authors.forename: Levi H C
authors.initials: LH
authors.lastname: Makala
authors.forename: Andy
authors.initials: A
authors.lastname: Muir
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
mesh_terms: D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit