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Expansion of a unique T cell subset Th40 describes a commonality in type 1 diabetes and MS
Author(s) -
Wagner David H,
Waid Dan M,
Vaitaitis Gisela M,
Pennock Nathan D,
Wagner Becky,
Corboy John,
Gottlieb Peter
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.667.26
Subject(s) - immunology , type 1 diabetes , cxcr3 , autoimmunity , cd8 , autoimmune disease , population , multiple sclerosis , biology , medicine , antigen , chemokine , chemokine receptor , endocrinology , diabetes mellitus , immune system , antibody , environmental health
We have described a unique T cell subset defined by CD4 lo and CD40 expression (Th40) that is significantly expanded in peripheral blood of T1D but not control or T2D subjects. Because Th40 cells may be a sub‐population where pathogenic T cells may arise, we examined Th40 cells in other disease models including Multiple Sclerosis (MS). Etiology of the autoimmunity in animal models suggests a prominent role for CD8+ and CD4+ T cells. We compared Th40 cells from T1D, MS, T2D and non‐autoimmune controls. Th40 levels from T1D subjects were significantly (p = 10 −17 ) elevated compared to T2D or non‐autoimmune controls. Interestingly as in T1D, Th40 levels were significantly elevated in MS subjects compared to controls including healthy siblings. Th40 expansion occurs in T1D subjects carrying the high risk HLA DR3 or DR4 haplotypes but, T1D subjects who do not carry either DR3 or DR4 haplotypes still have an expanded percentage of Th40 cells. A portion of Th40 cells from T1D subjects proliferates when exposed to diabetes‐associated self‐antigens. Th40 cells from T1D produce pro‐inflammatory cytokines including IFNγ, TNFα and IL‐6. When Th1‐associated chemokine receptors, CXCR3 and CCR5 are examined, Th40 cells from T1D preferentially express CXCR3, while Th40 cells from MS subjects do not. In contrast, T1D Th40 cells do not express CCR5 but Th40 cells from non‐autoimmune subjects do. These data demonstrate demonstrable differences in Th40 cells between autoimmune and non‐autoimmune subjects and importantly within distinct autoimmune diseases.