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. IFNγ-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.
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6 December 2004
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November 22 2004
Cytolytic CD8+ T Cells Recognizing CFP10 Are Recruited to the Lung after Mycobacterium tuberculosis Infection
Arati B. Kamath,
Arati B. Kamath
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
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Joshua Woodworth,
Joshua Woodworth
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
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Xiaowei Xiong,
Xiaowei Xiong
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
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Chad Taylor,
Chad Taylor
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
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Yu Weng,
Yu Weng
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
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Samuel M. Behar
Samuel M. Behar
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
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Arati B. Kamath
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
Joshua Woodworth
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
Xiaowei Xiong
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
Chad Taylor
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
Yu Weng
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
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: [email protected]
Abbreviations used in this paper: β2m, β2 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.
Received:
August 19 2004
Accepted:
October 25 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2004
J Exp Med (2004) 200 (11): 1479–1489.
Article history
Received:
August 19 2004
Accepted:
October 25 2004
Citation
Arati B. Kamath, Joshua Woodworth, Xiaowei Xiong, Chad Taylor, Yu Weng, Samuel M. Behar; Cytolytic CD8+ T Cells Recognizing CFP10 Are Recruited to the Lung after Mycobacterium tuberculosis Infection . J Exp Med 6 December 2004; 200 (11): 1479–1489. doi: https://doi.org/10.1084/jem.20041690
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