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Cytotoxic T Lymphocytes in Resistance to Tuberculosis

  • Chapter
Mechanisms of Lymphocyte Activation and Immune Regulation VII

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 452))

Summary

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-XD8- 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.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, 10461, USA

    Richard J. Mazzaccaro

  2. Institut für Klinische Mikrobiologie, Immunologie, und Hygiene, Wasserturmstr. 3, D-91054, Erlangen, Germany

    Steffen Stenger

  3. Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts, 01655, USA

    Kenneth L. Rock

  4. Lymphocyte Biology Section, Department of Rheumatology and Immunology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA

    Steven A. Porcelli & Michael B. Brenner

  5. Division of Dermatology and Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California, 90095, USA

    Robert L. Modlin

  6. Howard Hughes Medical Institute, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461, USA

    Dr. Barry R. Bloom

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  1. Richard J. Mazzaccaro
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  2. Steffen Stenger
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  3. Kenneth L. Rock
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  4. Steven A. Porcelli
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  5. Michael B. Brenner
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  6. Robert L. Modlin
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  7. Dr. Barry R. Bloom
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Correspondence to Barry R. Bloom .

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Editors and Affiliations

  1. University of California, Irvine, Irvine, California, USA

    Sudhir Gupta

  2. National Institutes of Health, Bethesda, Maryland, USA

    Alan Sher

  3. Emory University, Atlanta, Georgia, USA

    Rafi Ahmed

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Mazzaccaro, R.J. et al. (1998). Cytotoxic T Lymphocytes in Resistance to Tuberculosis. In: Gupta, S., Sher, A., Ahmed, R. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VII. Advances in Experimental Medicine and Biology, vol 452. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5355-7_11

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  • DOI: https://doi.org/10.1007/978-1-4615-5355-7_11

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