Cytotoxic T lymphocytes in resistance to tuberculosis

Richard J. Mazzaccaro, Steffen Stenger, Kenneth L. Rock, Steven A. Porcelli, Michael B. Brenner, Robert L. Modlin, Barry R. Bloom

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Recent experimental evidence has suggested T cells recognizing antigens in the context of both classical MHC class I and nonclassical class I-like molecules contribute to protective responses against Mycobacterium tuberculosis (MTB) infection. Our aims were to characterize both types of T cells, and to explore the basis of communication between the tubercle bacilli and the MHC class I pathway of the host macrophage. A model system was developed using exogenously added ovalbumin as a surrogate antigen to study presentation by MTB-infected macrophages. Viable, virulent MTB and closely related mycobacterial species facilitated the presentation of ovalbumin on MHC class I molecules to CD8+ cytolytic T cells that was dependent upon the cytosolic transport of peptides, implying communication between the MTB phagosome and the host cell cytoplasm: MHC class I presentation of soluble antigens was mimicked by Listeria monocytogenes, which grows within the host cell cytoplasm, as well as its purified hemolysin. We have also characterized T cells that recognize nonpeptide MTB antigens presented by CD1 molecules. CD1-restricted T cells demonstrated to lyse macrophages infected with virulent MTB were divided into distinct subsets based on surface phenotype (CD4-CD8- versus CD8+) and cytotoxicity mechanism (Fas receptor-mediated versus granule exocytosis). A functional consequence of these two mechanisms was observed that while both subsets lysed infected macrophages, only those T cells utilizing the granule exocytosis pathway were able to reduce viability of intracellular MTB.

Original languageEnglish (US)
Pages (from-to)85-101
Number of pages17
JournalAdvances in experimental medicine and biology
Volume452
StatePublished - Oct 29 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Mazzaccaro, R. J., Stenger, S., Rock, K. L., Porcelli, S. A., Brenner, M. B., Modlin, R. L., & Bloom, B. R. (1998). Cytotoxic T lymphocytes in resistance to tuberculosis. Advances in experimental medicine and biology, 452, 85-101.