The Journal of Experimental Medicine
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Published online 22 November 2004 doi:10.1084/jem.20041690
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 11, 1479-1489
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Cytolytic CD8+ T Cells Recognizing CFP10 Are Recruited to the Lung after Mycobacterium tuberculosis Infection

Arati B. Kamath, Joshua Woodworth, Xiaowei Xiong, Chad Taylor, Yu Weng, and Samuel M. Behar

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

Address correspondence to Samuel M. Behar, Div. of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard University, Smith Bldg., Rm. 516C, One Jimmy Fund Way, Boston, MA 02115. Phone: (617) 525-1033; Fax: (617)-525-1010; email: sbehar{at}rics.bwh.harvard.edu

Optimum immunity against Mycobacterium tuberculosis requires both CD4+ and CD8+ T cells. In contrast with CD4+ T cells, few antigens are known that elicit CD8+ T cells during infection. CD8+ T cells specific for culture filtrate protein-10 (CFP10) are found in purified protein derivative positive donors, suggesting that CFP10 primes CD8+ T cells in vivo. Using T cells from M. tuberculosis–infected mice, we identified CFP10 epitopes recognized by CD8+ T cells and CD4+ T cells. CFP10-specific T cells were detected as early as week 3 after infection and at their peak accounted for up to 30% of CD8+ T cells in the lung. IFN{gamma}-producing CD8+ and CD4+ T cells recognizing CFP10 epitopes were preferentially recruited to the lungs of M. tuberculosis–infected mice. In vivo cytolytic activity of CD8+ T cells specific for CFP10 and TB10.3/10.4 proteins was detected in the spleen, pulmonary lymph nodes, and lungs of infected mice. The cytolytic activity persisted long term and could be detected 260 d after infection. This paper highlights the cytolytic function of antigen-specific CD8+ T cells elicited by M. tuberculosis infection and demonstrates that large numbers of CFP10-specific cytolytic CD8+ T cells are recruited to the lung after M. tuberculosis infection.

Key Words: bacterial infection • T lymphocytes • cytotoxicity • H-2Kk haplotype • tetramers

Abbreviations used in this paper: ß2m, ß2 microglobulin; aa, amino acid; ANOVA, analysis of variance; BCG, bacillus Calmette-Guerin; CFP10, culture filtrate protein-10; ESAT-6, early secretory antigen target-6; PLN, pulmonary LN.


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