T cells reactive to a single immunodominant self-restricted allopeptide induce skin graft rejection in mice

Anna Valujskikh, Damir Matesic, Anita Gilliam, Donald Anthony, Tarriq M. Haqqi, Peter S. Heeger

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Alloreactive T lymphocytes can respond to foreign MHC complexed with foreign peptides through the direct pathway of allorecognition and can additionally recognize allopeptides expressed in the context of recipient (self) MHC through the indirect pathway. To better elucidate how indirect pathway-responsive CD4+ T cells mediate allograft rejection, we isolated and characterized a TH1 T cell line from BALB/c recipients of B10.A skin that responds to a defined immunodominant, self-restricted allopeptide, I- Aβ(k)58-71. When transferred into BALB/c severe combined immunodeficiency recipients of B10.A skin allografts, this cell line specifically induced a form of skin graft rejection characterized by the presence of TH1 cytokines, macrophage infiltration, and extensive fibrosis. Recall immune responses and immunofluorescence of the rejecting skin revealed only the presence of the peptide-specific T cells within the recipient animals, with no evidence of a direct pathway alloresponse. These studies demonstrate that T cells reactive to a single serf-restricted allopeptide can mediate a form of allogeneic skin graft rejection that exhibits characteristics of a chronic, fibrosing process.

Original languageEnglish
Pages (from-to)1398-1407
Number of pages10
JournalJournal of Clinical Investigation
Volume101
Issue number6
DOIs
StatePublished - 15 Mar 1998
Externally publishedYes

Keywords

  • Cellular immunity
  • Cytokines
  • Graft rejection
  • T lymphocytes
  • Transplantation immunology

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