Long-term control of Mycobacterium tuberculosis infection is mediated by dynamic immune responses

Vanja Lazarevic, Dawn Nolt, Jo Anne L. Flynn

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

The primary goal of this study was to determine how chronic exposure to Ag influences the functionality of Mycobacterium tuberculosis-specific T cell responses. The frequency of IFN-γ-producing effector CD4+ and CD8+ T cells dynamically changed during persistent M. tuberculosis infection. CD8+ T cells used differential effector functions during acute and chronic phases of the immune response, where CD8+ T cells produced negligible amounts of IFN-α early in infection, but switched to cytokine production during the chronic stage of infection. Using limiting dilution analysis, CD8+ T cells isolated during the initial phase of infection demonstrated lytic potential, but this waned in the chronic stage. The apparent loss of cytotoxic activity was not associated with the lack of perforin. Ag dose could potentially govern the functional program of CD8 + T cells. Collectively, these results depict a host immune response mounted against M. tuberculosis of a significantly more dynamic nature than previously recognized.

Original languageEnglish (US)
Pages (from-to)1107-1117
Number of pages11
JournalJournal of Immunology
Volume175
Issue number2
DOIs
StatePublished - Jul 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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