Protective HIV-specific CD8⁺ T cells evade T_reg cell suppression

 Shokrollah Elahi et al. 2011. Nat. Med. 17(8):989-995

Speaker: Wei-Hung Lin(林韋宏)                                  Time: 14:00~15:00, Dec. 14, 2011

Commentator: Dr. Shian-Wei Wang (王憲威老師)      Place: Room 601

Abstract

HIV infection usually results in progressive depletion of CD4⁺ T cells and consequent development of AIDS. However, in a small group of HIV-infected individuals, known as long-term nonprogressors (LTNPs), the viral load can be kept low and the CD4⁺ T cell counts are sustained. The well control of HIV in LTNPs has been associated with some specific human leukocyte antigens (HLAs), among which HLA-B*57 and HLA-B*27 alleles are overrepresented. CD8⁺ T cells restricted by HLA-B*57 or -B*27 may account for the effective HIV control and AIDS-free survival of LTNPs, but the mechanism is still unkown^1,2. In this article, the authors show that HIV-specific, HLA-B*57/B*27-restricted CD8⁺ T cells are more resistant to suppression by Treg cells than HIV-specific CD8⁺ T cells restricted by other HLA alleles. Proliferation of the HLA-B*57/B*27-restrictedCD8⁺ T cells is not inhibited by Treg-expressed galectin-9(Gal-9) because of their low expression of a galectin-9 receptor, T cell immunoglobulin domain and mucin domain-3(Tim-3). In addition, HLA-B*57/B*27- restricted CD8⁺ T cells can evade Treg-mediated suppression by directly killing Treg cells in a granzyme B-dependent manner. Notably, HLA-B*27-restricted CD8⁺ T cells against other chronic viruses are also resistant to Treg-‍mediated suppression, suggesting that these HLA alleles benefit control of chronic virus infection. Intriguingly, HLA-B*57/B*27-positive individuals have lower numbers of circulating Treg cells regardless of HIV infection, which may explain association of these HLA alleles with some autoimmune diseases. Therefore, HLA-B*57 and HLA-B*27 alleles seem to act as a double-edged sword: one for infection control but the other for autoimmunity.

References

1. Dinges, W.L. et al. Virus-specific CD8⁺ T cell responses better define HIV disease progression than HLA genotype. J. Virol. 84, 4461–4468 (2010).

2. Horton, H. et al. Preservation of T cell proliferation restricted by protective HLA alleles is critical for immune control of HIV-1 infection. J. Immunol. 177, 7406–7415 (2006).