Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection..pdf (2.15 MB)
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Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection.

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journal contribution
posted on 05.04.2016, 09:26 by E. Torrado, J. J. Fountain, M. Liao, M. Tighe, W. W. Reiley, R. P. Lai, G. Meintjes, John E. Pearl, X. Chen, D. E. Zak, E. G. Thompson, A. Aderem, N. Ghilardi, A. Solache, K. K. McKinstry, T. M. Strutt, R. J. Wilkinson, S. L. Swain, A. M. Cooper
CD4+ T cells mediate protection against Mycobacterium tuberculosis (Mtb); however, the phenotype of protective T cells is undefined, thereby confounding vaccination efforts. IL-27 is highly expressed during human tuberculosis (TB), and absence of IL-27R (Il27ra) specifically on T cells results in increased protection. IL-27R deficiency during chronic Mtb infection does not impact antigen-specific CD4+ T cell number but maintains programmed death-1 (PD-1), CD69, and CD127 expression while reducing T-bet and killer cell lectin-like receptor G1 (KLRG1) expression. Furthermore, T-bet haploinsufficiency results in failure to generate KLRG1+, antigen-specific CD4+ T cells, and in improved protection. T cells in Il27ra(-/-) mice accumulate preferentially in the lung parenchyma within close proximity to Mtb, and antigen-specific CD4+ T cells lacking IL-27R are intrinsically more fit than intact T cells and maintain IL-2 production. Improved fitness of IL-27R-deficient T cells is not associated with increased proliferation but with decreased expression of cell death-associated markers. Therefore, during Mtb infection, IL-27R acts intrinsically on T cells to limit protection and reduce fitness, whereas the IL-27R-deficient environment alters the phenotype and location of T cells. The significant expression of IL-27 in TB and the negative influence of IL-27R on T cell function demonstrate the pathway by which this cytokine/receptor pair is detrimental in TB.

History

Citation

Journal of Experimental Medicine, 2015, 212 (9), pp. 1449-1463

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Journal of Experimental Medicine

Publisher

Rockefeller University Press

issn

0022-1007

eissn

1540-9538

Acceptance date

21/07/2015

Copyright date

2015

Available date

05/04/2016

Publisher version

http://jem.rupress.org/content/212/9/1449

Language

en