HLA-class I-specific inhibitory receptors in HIV-1 infection

Hum Immunol. 2000 Jan;61(1):74-81. doi: 10.1016/s0198-8859(99)00169-x.

Abstract

One of the most characteristic and, at the same time, puzzling features of the cellular immune response towards HIV-1 is represented by an early vigorous HIV-specific CD8+ CTL response that does not prevent disease progression in the vast majority of patients. In this context, there is a striking mismatch over the course of disease progression between increasing numbers of activated CD8+ T cells and apparent decrease of virus-specific CD8+ CTLs. Inhibitory NK receptors (iNKRs) specific for HLA class I molecules can be expressed on CD8+ T-cells of healthy individuals and deliver inhibitory signals that determine decreased CTL function. Their expression on CD8+ CTL may be induced by IL-15 or TGFP in vitro, and may represent an important regulatory function for the fine-tuning of the antigen-specific T cell response against tumors and intracytoplasmic pathogens. In HIV-1 infected patients, relevant proportions of peripheral blood CD8+ T lymphocytes express iNKRs belonging to the Ig superfamily (p58/p70/p140) and CD94/NKG2A. Presence of iNKRs on CD8+ CTLs impairs HIV-1-specific cytolytic activity in vitro and may allow uncontrolled viral replication and spread following functional inhibition of CTL effectors in infected patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Killer Cells, Natural / immunology*
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Receptors, KIR
  • Receptors, KIR2DL3
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Histocompatibility Antigens Class I
  • KIR2DL3 protein, human
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL3