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Protective HIV-specific CD8+ T cells evade Treg cell suppression.
Title | Protective HIV-specific CD8+ T cells evade Treg cell suppression. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Elahi, S, Dinges, WL, Lejarcegui, N, Laing, KJ, Collier, AC, Koelle, DM, McElrath, JM, Horton, H |
Journal | Nat Med |
Volume | 17 |
Issue | 8 |
Pagination | 989-95 |
Date Published | 2011 Aug |
ISSN | 1546-170X |
Keywords | CD8-Positive T-Lymphocytes, Cell Death, Epitope Mapping, Female, Flow Cytometry, Gene Expression Regulation, HIV Infections, HIV-1, HLA-B Antigens, HLA-B27 Antigen, Humans, Male, Membrane Proteins, Polymorphism, Single Nucleotide, RNA Interference, RNA, Small Interfering, T-Lymphocytes, Regulatory |
Abstract | Specific human leukocyte antigens (HLAs), notably HLA-B*27 and HLA-B*57 allele groups, have long been associated with control of HIV-1. Although the majority of HIV-specific CD8(+) T cells lose proliferative capacity during chronic infection, T cells restricted by HLA-B*27 or HLA-B*57 allele groups do not. Here we show that CD8(+) T cells restricted by 'protective' HLA allele groups are not suppressed by T(reg) cells, whereas, within the same individual, T cells restricted by 'nonprotective' alleles are highly suppressed ex vivo. This differential sensitivity of HIV-specific CD8(+) T cells to T(reg) cell-mediated suppression correlates with their expression of the inhibitory receptor T cell immunoglobulin domain and mucin domain 3 (Tim-3) after stimulation with their cognate epitopes. Furthermore, we show that HLA-B*27- and HLA-B*57-restricted effectors also evade T(reg) cell-mediated suppression by directly killing T(reg) cells they encounter in a granzyme B (GzmB)-dependent manner. This study uncovers a previously unknown explanation for why HLA-B*27 and HLA-B*57 allele groups are associated with delayed HIV-1 disease progression. |
DOI | 10.1038/nm.2422 |
Alternate Journal | Nat. Med. |
PubMed ID | 21765403 |