Ethylenecarbodiimide-treated splenocytes carrying male CD4 epitopes confer histocompatability Y chromosome antigen transplant protection by inhibiting CD154 upregulation

Aaron J. Martin, Derrick McCarthy, Carl Waltenbaugh, Gwen Goings, Xunrong Luo, Stephen D. Miller

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

In humans and certain strains of laboratory mice, male tissue is recognized as nonself and destroyed by the female immune system via recognition of histocompatibility Y chromosome Ag (Hya). Male tissue destruction is thought to be accomplished by CTLs in a helper-dependent manner. We show that graft protection induced with the immunodominant Hya-encoded CD4 epitope (Dby) attached to female splenic leukocytes (Dby-SPs) with the chemical cross-linker ethylenecarbodiimide significantly, and often indefinitely, prolongs the survival of male skin graft transplants in an Ag-specific manner. In contrast, treatments with the Hya CD8 epitopes (Uty-/Smcy-SPs) failed to prolong graft survival. Dby-SP-tolerized CD4+ T cells fail to proliferate, secrete IFN-γ, or effectively prime a CD8 response in recipients of male grafts. Ag-coupled splenocyte treatment is associated with defective CD40-CD40L interactions as demonstrated by the observation that CD4 cells from treated animals exhibit a defect in CD40L upregulation following in vitro Ag challenge. Furthermore, treatment with an agonistic anti-CD40 Ab at the time of transplantation abrogates protection from graft rejection. Interestingly, anti-CD40 treatment completely restores the function of Dby-specific CD4 cells but not Uty- or Smcy-specific CD8 cells.

Original languageEnglish (US)
Pages (from-to)3326-3336
Number of pages11
JournalJournal of Immunology
Volume185
Issue number6
DOIs
StatePublished - Sep 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Ethylenecarbodiimide-treated splenocytes carrying male CD4 epitopes confer histocompatability Y chromosome antigen transplant protection by inhibiting CD154 upregulation'. Together they form a unique fingerprint.

Cite this