NDLI: Multiple Inflammatory Cytokines Converge To Regulate CD8+ T Cell Expansion and Function during Tuberculosis.

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Multiple Inflammatory Cytokines Converge To Regulate CD8+ T Cell Expansion and Function during Tuberculosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nunes-Alves, Cláudio Booty, Matthew G. Carpenter, Stephen M. Jayaraman, Pushpa Behar, Samuel M.
Description	Author Affiliation: Booty MG ( Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655); Nunes-Alves C ( Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655); Carpenter SM ( Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655); Jayaraman P ( Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655); Behar SM ( Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655)
Abstract	The differentiation of effector CD8(+) T cells is a dynamically regulated process that varies during different infections and is influenced by the inflammatory milieu of the host. In this study, we define three signals regulating CD8(+) T cell responses during tuberculosis by focusing on cytokines known to affect disease outcome: IL-12, type I IFN, and IL-27. Using mixed bone marrow chimeras, we compared wild-type and cytokine receptor knockout CD8(+) T cells within the same mouse following aerosol infection with Mycobacterium tuberculosis. Four weeks postinfection, IL-12, type 1 IFN, and IL-27 were all required for efficient CD8(+) T cell expansion in the lungs. We next determined if these cytokines directly promote CD8(+) T cell priming or are required only for expansion in the lungs. Using retrogenic CD8(+) T cells specific for the M. tuberculosis Ag TB10.4 (EsxH), we observed that IL-12 is the dominant cytokine driving both CD8(+) T cell priming in the lymph node and expansion in the lungs; however, type I IFN and IL-27 have nonredundant roles supporting pulmonary CD8(+) T cell expansion. Thus, IL-12 is a major signal promoting priming in the lymph node, but a multitude of inflammatory signals converge in the lung to promote continued expansion. Furthermore, these cytokines regulate the differentiation and function of CD8(+) T cells during tuberculosis. These data demonstrate distinct and overlapping roles for each of the cytokines examined and underscore the complexity of CD8(+) T cell regulation during tuberculosis.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	196
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2016-02-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cd8-positive T-lymphocytes Immunology Cytokines Lymphocyte Activation Tuberculosis, Pulmonary Animals Cell Differentiation Disease Models, Animal Flow Cytometry Mice Mice, Inbred C57bl Mice, Knockout Oligonucleotide Array Sequence Analysis Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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