Early emergence of CD8(+) T cells primed for production of type 1 cytokines in the lungs of Mycobacterium tuberculosis-infected mice.
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-gamma). However, a difference in in vivo IFN-gamma production by T cells was observed with approximately 12% of CD4(+) T cells and approximately 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-gamma is produced by CD4(+) T cells, cytokine-producing CD8(+) T cells are readily available when triggered by the appropriate stimuli.
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
N V
NV
Serbina
J L
JL
Flynn
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D014376:Tuberculosis / Q000276:immunology*
D016207:Cytokines; D007371:Interferon-gamma