Endogenous memory CD8 T cells are activated within cardiac allografts without mediating rejection

K. Setoguchi, Y. Hattori, S. Iida, W. M. Baldwin, R. L. Fairchild

Research output: Contribution to journalArticlepeer-review

Abstract

Endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts within 12-24 h posttransplant in mice and are activated to proliferate and produce IFN-γ. To more accurately assess the graft injury directly imposed by these endogenous memory CD8 T cells, we took advantage of the ability of anti-LFA-1 mAb given to allograft recipients on days 3 and 4 posttransplant to inhibit the generation of primary effector T cells. When compared to grafts from IgG-treated recipients on day 7 posttransplant, allografts from anti-LFA-1 mAb-treated recipients had increased numbers of CD8 T cells but these grafts had marked decreases in expression levels of mRNA encoding effector mediators associated with graft injury and decreases in donor-reactive CD8 T cells producing IFN-γ. Despite this decreased activity within the allograft, CD8 T cells in allografts from recipients treated with anti-LFA-1 mAb continued to proliferate up to day 7 posttransplant and did not upregulate expression of the exhaustion marker LAG-3 but did have decreased expression of ICOS. These results indicate that endogenous memory CD8 T cells infiltrate and proliferate in cardiac allografts in mice but do not express sufficient levels of functions to mediate overt graft injury and acute rejection. Using strategies that permit the infiltration of endogenous memory CD8 T cells into cardiac allografts but delay the development of donor-reactive primary effector T cells in the recipient spleen, these studies indicate the inability of endogenous memory CD8 T cells to express sufficient function to provoke overt graft injury and failure.

Original languageEnglish (US)
Pages (from-to)2293-2307
Number of pages15
JournalAmerican Journal of Transplantation
Volume13
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • Cardiac allograft
  • memory
  • T cell activation/inactivation
  • T cell graft infiltration

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

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