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.
View: Text | PDF
Research Article Immunology Article has an altmetric score of 1

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

×

Figure 1

In vitro model of CD27-mediated T cell survival.

Options: View larger image (or click on image) Download as PowerPoint
In vitro model of CD27-mediated T cell survival. (A) A mouse fibroblast ...
(A) A mouse fibroblast line engineered to express the OVA257-264 peptide in the context of H-2Kb (26) was used as aAPCs for cognate OT-I CD8+ T cell priming in vitro. These cells were transduced to express CD70 and/or CD80 and flow cytometrically sorted on equal H-2Kb expression as schematically presented in the drawing. Histograms show CD80 and CD70 expression in MFI on the 4 indicated aAPC lines used. (B and C) Naive CFSE-labeled WT or Cd27–/– OT-I T cells were cocultured with the indicated aAPCs. Cells were counted and stained with TO-PRO-3, and CFSE dilution was determined by flow cytometry at 72 or 96 hours. (B) Left: Percentage of total H-2Kb/OVA257-264 tetramer+ CD8+ OT-I cells in each cell division, as reflected by CFSE fluorescence intensity. Right: Absolute number of OT-I cells per division. Data are mean values + SEM of 4 samples and are representative of 3 independent experiments.*P < 0.005, WT versus Cd27–/– (t test). (C) The number of live OT-I cells present at 72 or 96 hours after priming, shown as percentage of control (WT + aAPC;CD70/CD80). Data are mean + SEM of 4 independent experiments.**P < 0.0005 versus control (t test).