title: Ethylenecarbodiimide-treated splenocytes carrying male CD4 epitopes confer histocompatibility Y chromosome antigen transplant protection by inhibiting CD154 upregulation.
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-gamma, 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.
authors: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Aaron J
authors: AJ
authors: Martin
authors: Derrick
authors: D
authors: McCarthy
authors: Carl
authors: C
authors: Waltenbaugh
authors: Gwen
authors: G
authors: Goings
authors: Xunrong
authors: X
authors: Luo
authors: Stephen D
authors: SD
authors: Miller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D002234:Carbodiimides / Q000276:immunology* / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006182:H-Y Antigen / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012727:Sex Characteristics; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D015854:Up-Regulation / Q000276:immunology*; D014998:Y Chromosome / Q000276:immunology*
chemical_list: D002234:Carbodiimides; D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D023201:CD40 Ligand