CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production
Victor Peperzak, … , Elise A.M. Veraar, Jannie Borst
Victor Peperzak, … , Elise A.M. Veraar, Jannie Borst
Published December 1, 2009
Citation Information: J Clin Invest. 2010;120(1):168-178. https://doi.org/10.1172/JCI40178.
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Research Article Immunology

CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production

Abstract

Immunity to infections relies on clonal expansion of CD8+ T cells, their maintenance as effector CTLs, and their selection into a memory population. These processes rely on delivery of survival signals to activated CD8+ T cells. We here reveal the mechanism by which costimulatory CD27-CD70 interactions sustain survival of CD8+ effector T cells in infected tissue. By unbiased genome-wide gene expression analysis, we identified the Il2 gene as the most prominent CD27 target gene in murine CD8+ T cells. In vitro, CD27 directed IL-2 expression and promoted clonal expansion of primed CD8+ T cells exclusively by IL-2–dependent survival signaling. In mice intranasally infected with influenza virus, Cd27–/– CD8+ effector T cells displayed reduced IL-2 production, accompanied by impaired accumulation in lymphoid organs and in the lungs, which constitute the tissue effector site. Reconstitution of Cd27–/– CD8+ T cells with the IL2 gene restored their accumulation to wild-type levels in the lungs, but it did not rescue their accumulation in lymphoid organs. Competition experiments showed that the IL-2 produced under the control of CD27 supported effector CD8+ T cell survival in the lungs in an autocrine manner. We conclude that CD27 signaling directs the IL-2 production that is reportedly essential to sustain survival of virus-specific CTLs in nonlymphoid tissue.

Authors

Victor Peperzak, Yanling Xiao, Elise A.M. Veraar, Jannie Borst

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Figure 7

CD27 mediates effector CD8+ T cell survival via an autocrine IL-2 pathway.

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CD27 mediates effector CD8+ T cell survival via an autocrine IL-2 pathwa...
Nontransgenic Cd27–/– T cells retrovirally transduced with an IL-2IRESGFP vector or ev-YFP were mixed at a 1:1 ratio and transferred into Cd27–/– mice. At day 8 after influenza virus infection, cells extracted from DLN, spleen, and lung were enumerated, stained with mAb against CD8 and CD62L, and analyzed by flow cytometry. (A) The gating strategy used to detect the indicated cell populations. (B) Absolute numbers of GFP+ or YFP+ CD8+ CD62Llo/neg effector T cells (Teff). Data are mean + SEM of 3 mice. *P < 0.01 (t test). (C) Schematic representation of the CD27-driven autocrine pathway for IL-2 production at the tissue site (lung). CD70 on professional APCs triggers CD27 on the T cell, which induces Il2 gene expression. IL-2 drives survival via its receptor (IL-2R) on the same T cells.