Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance
Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance
Hye-Jung Kim et al. Nature 467:328-332, 2010
Speaker: Yung-Tsai Liou (劉勇材) Time: 14:10-15:00, Dec. 1, 2010
Commentator: Dr. Chi-Chang Shieh (謝奇璋 老師) Place: Room 601
Abstract
The immune system provides sophisticated protection from foreign pathogens and avoids attacking self-antigens. Previous studies in the 1980s have shown that CD8+ suppressor T cells recognize self-antigens presented by Qa-1 to maintain self tolerance. Murine Qa-1 (or human HLA-E) molecule belongs to MHC class Ib family and is expressed on immune cells, including T and B lymphocytes and dendritic cells1. The authors showed in this paper that Qa-1 was expressed on the surface of follicular B helper T cells (TFH) from the mice immunized with KLH/CFA. TFH cells could be found in the germinal center of secondary lymphoid organs, such as spleen, lymph nodes, and Peyer’s patches. The authors generated Qa-1(D227K) knock-in mice carrying mutant Qa-1 that could not bind to TCR/CD8 coreceptor, and detected high levels of autoantibodies in the serum and IgG deposition in the renal glomeruli from 4~6-month-old Qa-1(D227K) mice. The Qa-1(D227K) mice that were either immunized with KLH/CFA or infected with lymphocytic choriomeningitis virus (LCMV)-Armstrong showed increased autoantibody production, as compared with wild-type control mice. Adoptive transfer of wild-type B cells and ICOSL+ CD8+ Treg cells along with mutant Qa-1(D227K) CD4+ T cells to Rag2-/- mice caused higher autoantibody production than those with the wild-type CD4+ T cells after KLH/CFA challenge, indicating that ICOSL+ CD8+Treg cells could recognize antigen presented by Qa-1 on CD4+ T cells. A recent study showed that IL-15 is required for CD8+ T cell functions2. The authors demonstrated that Il15-/- CD8+ Treg cells failed to suppress autoantibody production. Moreover, anti-IL-15 antibody abrogated the suppressive activity of wild-type CD8+ Treg cells. In conclusion, CD8+ Treg cells recognize self-antigens presented by Qa-1 molecule, and suppress TFH-stimulated autoantibody production to maintain self tolerance.
References
1. Sarantopoulos S, Lu L, and Cantor H. Qa-1 restriction of CD8+ suppressor T cells. J. Clin. Invest. 114:1218–1221, 2004.
2. Mitchell DM, Ravkov EV, and Williams MA. Distinct roles for IL-2 and IL-15 in the differentiation and survival of CD8+ effector and memory T cells. J. Immunol. 184:6719–6730, 2010.