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Infection and Immunity, June 2003, p. 3076-3087, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3076-3087.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

T-Cell Responses to CD1-Presented Lipid Antigens in Humans with Mycobacterium tuberculosis Infection

Timo Ulrichs,1,2 D. Branch Moody,3 Ethan Grant,3 Stefan H. E. Kaufmann,2 and Steven A. Porcelli1*

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York,1 Department of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts,3 Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany2

Received 20 November 2002/ Returned for modification 6 January 2003/ Accepted 7 March 2003

CD1-restricted presentation of lipid or glycolipid antigens derived from Mycobacterium tuberculosis has been demonstrated by in vitro experiments using cultured T-cell lines. In the present work, the frequency of T-cell responses to natural mycobacterial lipids was analyzed in ex vivo studies of peripheral blood lymphocytes from human patients with pulmonary tuberculosis, from asymptomatic individuals with known contact with M. tuberculosis documented by conversion of their tuberculin skin tests, and from healthy tuberculin skin test-negative individuals or individuals vaccinated with Mycobacterium bovis BCG. Proliferation and gamma interferon enzyme-linked immunospot assays using peripheral blood lymphocytes and autologous CD1+ immature dendritic cells revealed that T cells from asymptomatic M. tuberculosis-infected donors responded with significantly greater magnitude and frequency to mycobacterial lipid antigen preparations than lymphocytes from uninfected healthy donors. By use of these methods, lipid-antigen-specific proliferative responses were minimally detectable or absent in blood samples from patients with active tuberculosis prior to chemotherapy but became detectable in blood samples drawn 2 weeks after the start of treatment. Lipid antigen-reactive T cells were detected predominantly in the CD4-enriched T-cell fractions of circulating lymphocytes, and anti-CD1 antibody blocking experiments confirmed the CD1 restriction of these T-cell responses. Our results provide further support for the hypothesis that lipid antigens serve as targets of the recall response to M. tuberculosis, and they indicate that CD1-restricted T cells responding to these antigens comprise a significant portion of the circulating pool of M. tuberculosis-reactive T cells in healthy individuals with previous exposure to M. tuberculosis.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Yeshiva University, Room 416 Forchheimer Building, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-3228. Fax: (718) 430-8711. E-mail: porcelli{at}aecom.yu.edu.

Editor: J. D. Clements

Infection and Immunity, June 2003, p. 3076-3087, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3076-3087.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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