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Title: Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection.
Authors: Torrado, E.
Fountain, J. J.
Liao, M.
Tighe, M.
Reiley, W. W.
Lai, R. P.
Meintjes, G.
Pearl, John E.
Chen, X.
Zak, D. E.
Thompson, E. G.
Aderem, A.
Ghilardi, N.
Solache, A.
McKinstry, K. K.
Strutt, T. M.
Wilkinson, R. J.
Swain, S. L.
Cooper, A. M.
First Published: 24-Aug-2015
Publisher: Rockefeller University Press
Citation: Journal of Experimental Medicine, 2015, 212 (9), pp. 1449-1463
Abstract: 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.
DOI Link: 10.1084/jem.20141520
ISSN: 0022-1007
eISSN: 1540-9538
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015, the authors. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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