Early Emergence of CD8 + T Cells Primed for Production of Type 1 Cytokines in the Lungs of Mycobacterium tuberculosis -Infected Mice

Abstract

ABSTRACT Several lines of evidence suggest that CD8 T cells are important in protection against tuberculosis. To understand the function of this cell population in the immune response against Mycobacterium tuberculosis , T cells from lungs of M. tuberculosis -infected mice were examined by flow cytometry. The kinetics of the appearance of CD8 T cells in lungs of infected mice closely paralleled that of CD4 T cells. Both CD4 + and CD8 + T cells displaying an activated phenotype were found in the lungs as early as 1 week postinfection. By 2 weeks, total cell numbers in the lungs had tripled and percentages of T cells were increased two- to threefold; the percentages of CD4 + T cells were ca. twofold higher than those of CD8 + T cells. Short-term stimulation with M. tuberculosis -infected antigen-presenting cells induced cytokine production by primed CD4 + and CD8 + T cells. Intracellular cytokine staining revealed that 30% ± 5% of CD4 + and 23% ± 4% of CD8 + T cells were primed for production of gamma interferon (IFN-γ). However, a difference in in vivo IFN-γ production by T cells was observed with ∼12% of CD4 + T cells and ∼5% of CD8 + T cells secreting cytokine in the lungs at any given time during infection. The data presented indicate that although early in infection the majority of IFN-γ is produced by CD4 + T cells, cytokine-producing CD8 + T cells are readily available when triggered by the appropriate stimuli.