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

Nat Med. 2011 Jul 17;17(8):989-95. doi: 10.1038/nm.2422.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Death / immunology
  • Epitope Mapping
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology*
  • HLA-B27 Antigen / genetics
  • HLA-B27 Antigen / immunology*
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Male
  • Membrane Proteins / immunology
  • Polymorphism, Single Nucleotide / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics
  • T-Lymphocytes, Regulatory / virology*


  • HAVCR2 protein, human
  • HLA-B Antigens
  • HLA-B27 Antigen
  • HLA-B57 antigen
  • Hepatitis A Virus Cellular Receptor 2
  • Membrane Proteins
  • RNA, Small Interfering