The strength of cell-mediated xenograft rejection in the mouse is due to the CD4+ indirect response.
Previous studies have shown that CD4+ T cells are responsible for the great strength of cell-mediated xenograft rejection in the mouse. In vitro studies have suggested that this CD4+ response is to xenogeneic antigens that are presented indirectly. The present studies were carried out in order to determine whether the strength of cell-mediated xenograft rejection in vivo is dependent on the CD4+ indirect response. We grafted pig skin onto mice that express class II MHC antigens only on their thymic epithelial cells (II-4+ mice). These mice have normal numbers of functional peripheral CD4+ T cells; however they lack class II MHC expression on their antigen presenting cells and are thus incapable of mounting a CD4+ T cell-mediated indirect response. Xenograft survival was prolonged on these mice. Furthermore, administration of cyclosporine and anti-CD8 monoclonal antibodies to II-4+ recipients prolonged xenograft survival to at least the same extent as allograft survival, demonstrating that the strength of cell-mediated xenograft rejection resides in the CD4+ indirect response. Despite the increased survival time, xenograft rejection still occurred in the absence of the indirect pathway. Depletion of the II-4+ recipients of their CD4+ T cell population prolonged xenograft survival even further, suggesting the presence of a weaker CD4+ direct mechanism which was virtually undetectable in vitro.
Chitilian
H V
HV
Transplantation Unit, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Laufer
T M
TM
Stenger
K
K
Shea
S
S
Auchincloss
H
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000009:adverse effects / Q000276:immunology; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous / Q000009:adverse effects* / Q000276:immunology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D016572:Cyclosporine