Mycobacterium tuberculosis-specific CD8+ T Cells Preferentially Recognize Heavily Infected Cells

Deborah A. Lewinsohn, Amy S. Heinzel, James M. Gardner, Liqing Zhu, Mark R. Alderson, David M. Lewinsohn

Research output: Contribution to journalArticle

97 Scopus citations

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-γ and tumor necrosis factor-α. 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-γ, 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.

Original languageEnglish (US)
Pages (from-to)1346-1352
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume168
Issue number11
DOIs
StatePublished - Dec 1 2003

Keywords

  • Antigen presentation
  • CD4-positive T lymphocytes
  • CD8-positive T lymphocytes
  • Cytotoxic T lymphocytes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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