Enhanced requirement for TNFR2 in graft rejection mediated by low-affinity memory CD8+ T cells during heterologous immunity

Scott M. Krummey, Ching Wen Chen, Sara A. Guasch, Danya Liu, Maylene Wagener, Christian P. Larsen, Mandy L. Ford

Research output: Contribution to journalArticlepeer-review

Abstract

The affinity of a TCR binding to peptide:MHC profoundly impacts the phenotype and function of effector and memory cell differentiation. Little is known about the effect of low-affinity priming on memory cell generation and function, which is particularly important in heterologous immunity, when microbe-specific T cells cross-react with allogeneic Ag and mediate graft rejection. We found that low-affinity-primed memory CD8+ T cells produced high levels of TNF ex vivo in response to heterologous rechallenge compared with high-affinity-primed memory T cells. Low-affinity secondary effectors significantly upregulated TNFR2 on the cell surface and contained a higher frequency of TNFR2hi proliferating cells. Low-affinity-primed secondary effectors concurrently downregulated TNF production. Importantly, blockade of TNFR2 attenuated graft rejection in low-but not high-affinity-primed animals. These data establish a functional connection between TNF signaling and TCR-priming affinity and have implications for the immunomodulation of pathogenic T cell responses during transplantation.

Original languageEnglish (US)
Pages (from-to)2009-2015
Number of pages7
JournalJournal of Immunology
Volume197
Issue number5
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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