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

J Clin Invest. 2010 Jan;120(1):168-78. doi: 10.1172/JCI40178. Epub 2009 Dec 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD27 Ligand / physiology
  • Cell Survival
  • Cells, Cultured
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology*
  • Receptors, Interleukin-2 / physiology
  • T-Lymphocytes, Cytotoxic / physiology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology*


  • CD27 Ligand
  • Interleukin-2
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interferon-gamma