Mycobacterium tuberculosis-specific CD8+ T cells preferentially recognize heavily infected cells

Am J Respir Crit Care Med. 2003 Dec 1;168(11):1346-52. doi: 10.1164/rccm.200306-837OC. Epub 2003 Sep 11.

Abstract

Both CD4+ and CD8+ T cells are important for successful immunity to tuberculosis and have redundant effector functions, such as cytolysis and release of potent antimycobacterial cytokines such as interferon-gamma and tumor necrosis factor-alpha. We hypothesized that CD8+ T cells play a unique role in host defense to Mycobacterium tuberculosis infection as well. Possibilities include preferential and/or enhanced release of granular constituents and/or preferential recognition of heavily infected cells. Utilizing human, Mycobacterium tuberculosis-specific, CD4+ and CD8+ T cell clones, we demonstrate that, after recognition of antigen-presenting cells displaying peptide antigen, CD4+ T cells preferentially release interferon-gamma, whereas CD8+ T cells preferentially lyse antigen-presenting cells. Furthermore, utilizing dendritic cells infected with Mycobacterium tuberculosis expressing green fluorescent protein, we show that CD8+ T cells preferentially recognize heavily infected cells that constitute the minority of infected cells. These data support the hypothesis that the central role of CD8+ T cells in the control of infection with Mycobacterium tuberculosis may be that of surveillance; in essence, recognition of cells in which the containment of Mycobacterium tuberculosis is no longer effective.

Publication types

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

MeSH terms

  • Antigens, Bacterial / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Exocytosis / immunology
  • HLA Antigens / immunology
  • HLA-B Antigens / immunology
  • HLA-B14 Antigen
  • HLA-B44 Antigen
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / immunology
  • Lymphocyte Activation / immunology*
  • Mycobacterium tuberculosis / immunology*

Substances

  • Antigens, Bacterial
  • HLA Antigens
  • HLA-B Antigens
  • HLA-B14 Antigen
  • HLA-B44 Antigen
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • Mycobacterium tuberculosis antigens
  • Interferon-gamma