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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

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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 3

CD27 promotes IL-2 expression in effector CD8+ T cells upon influenza virus infection.

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CD27 promotes IL-2 expression in effector CD8+ T cells upon influenza vi...
Cd27+/– and Cd27–/– littermates were infected intranasally with influenza virus, and DLN, spleen, and lung were isolated at day 8 or 10 after infection. (A) The indicated organs were flow cytometrically analyzed for the presence of virus-specific effector CD8+ T cells on the basis of a CD8+, CD62Llo/neg, H-2Db/NP366-374 tetramer+ phenotype. Absolute numbers of cells are represented. (B and C) Total suspension cells extracted from the indicated organs were restimulated for 4 hours in vitro with NP366-374 peptide; stained for IFN-γ, IL-2, and CD8; and analyzed by flow cytometry. (B) Representative flow cytometric plot of spleen cells gated on CD8+ T cells. Numbers indicate the mean percentages (±SEM) of IL-2+ cells within the CD8+, IFN-γ+ population. (C) Numbers of IL-2+IFN-γ+CD8+ cells per organ. (A–C) Data are mean ± SEM from 4 mice. *P < 0.05, **P < 0.01 compared with Cd27+/– samples (t test).

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