IL-15 induces alloreactive CD28- Memory CD8 T cell proliferation and CTLA4-Ig resistant memory CD8 T cell activation

O. Traitanon, A. Gorbachev, J. J. Bechtel, K. S. Keslar, W. M. Baldwin, E. D. Poggio, R. L. Fairchild

Research output: Contribution to journalArticle

Abstract

The presence of CD28- memory CD8 T cells in the peripheral blood of renal transplant patients is a risk factor for graft rejection and resistance to CTLA-4Ig induction therapy. In vitro analyses have indicated poor alloantigen-induced CD28- memory CD8 T cell proliferation, raising questions about mechanisms mediating their clonal expansion in kidney grafts to mediate injury. Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28- memory CD8 T cell proliferation. Addition of IL-15, but not IL-2 or IL-7, to co-cultures of CD28- or CD28+ memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28- and enhanced CD28+ memory T cell proliferation. Proliferating CD28- memory CD8 T cells produced high amounts of interferon gamma and tumor necrosis factor alpha and expressed higher levels of the cytolytic marker CD107a than CD28+ memory CD8 T cells. CTLA-4Ig inhibited alloantigen-induced proliferation of CD28+ memory CD8 T cell proliferation but had no effect on alloantigen plus IL-15-induced proliferation of either CD28- or CD28+ memory CD8 T cells. These results indicate the ability of IL-15, a cytokine produced by renal epithelial during inflammation, to provoke CD28- memory CD8 T cell proliferation and to confer memory CD8 T cell resistance to CTLA-4Ig-mediated costimulation blockade. IL-15 induces the activation of alloreactive CD28 - memory CD8 T cells and confers resistance of alloreactive CD28 + memory CD8 T cells to CTLA-4Ig-mediated inhibition.

Original languageEnglish (US)
Pages (from-to)1277-1289
Number of pages13
JournalAmerican Journal of Transplantation
Volume14
Issue number6
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • belatacept
  • Costimulation
  • cytokines/cytokine receptors
  • immunosuppressant
  • T cell biology

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)
  • Medicine(all)

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