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Infection and Immunity, August 1999, p. 3980-3988, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Early Emergence of CD8+ T Cells Primed
for Production of Type 1 Cytokines in the Lungs of Mycobacterium
tuberculosis-Infected Mice
Natalya V.
Serbina, and
JoAnne L.
Flynn*
Department of Molecular Genetics and
Biochemistry, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania
Received 4 February 1999/Returned for modification 11 March
1999/Accepted 7 May 1999
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-
). However, a difference in in vivo IFN-
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-
is produced by
CD4+ T cells, cytokine-producing CD8+ T cells
are readily available when triggered by the appropriate stimuli.
*
Corresponding author. Mailing address: Department of
Molecular Genetics and Biochemistry, E1240 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. Phone: (412) 624-7743. Fax: (412) 624-1401. E-mail:
joanne{at}pop.pitt.edu.
Infection and Immunity, August 1999, p. 3980-3988, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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[Full Text]
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[Full Text]
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