Enhanced CD8 T cell cross-presentation by macrophages with targeted disruption of STAT3

Jason Brayer, Fengdong Cheng, Hongwei Wang, Pedro Horna, Ildefonso Vicente-Suarez, Javier Pinilla-Ibarz, Eduardo M. Sotomayor

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

CD8 T cell tolerance, once thought to be largely a result of clonal deletion, is now appreciated to be much more complex, additionally involving multiple permutations of partial loss of effector function in residual clonal populations. This is especially important in the context of tumor immunity, in which persistent tolerized cytotoxic CD8 T cells (CTL), if reactivated, could potentially mount a protective response. Previously we have shown that antigen-presenting cells (APCs) with a targeted disruption of STAT3 break tolerance in CD4 T cells. Here we evaluate the STAT3-defective APC in terms of its ability to induce a productive CTL response. Our data demonstrate that macrophages derived from conditional STAT3 knockout mice are superior to wild-type macrophages in terms of their ability to prime cognate CTL responses, and to cross-present tumor-derived antigen to CTLs in vitro. CTLs cultured with STAT3-deficient APCs demonstrated a stronger proliferative response and produced increased amounts of IFN-γ and TNF-α, all of which have been shown to be diminished in tumor-tolerized CD8 T cells. Targeting STAT3 signaling represents therefore an enticing strategy to augment CTL responses in the tumor-bearing host.

Original languageEnglish (US)
Pages (from-to)126-130
Number of pages5
JournalImmunology Letters
Volume131
Issue number2
DOIs
StatePublished - Jul 2010

Keywords

  • CD8
  • Cytotoxic
  • STAT3

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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