Role of CD4+ T cells in the rat to mouse cardiac xenotransplantation.
T cell subsets involved in rejection of xenografts were analyzed using a rat to mouse cardiac xenotransplant model. Proliferating response and interleulin-2 (IL-2) production in recipients' spleen cells were almost completely abrogated by elimination of L3T4+ T cells, but not by elimination of Lyt2.1+ T cells. Cytotoxic T lymphocyte (CTL) activities were mediated by both L3T4+ and Lyt2.1+ T cells with the help of IL-2-producing L3T4+ T cells. Administration of anti-L3T4 monoclonal antibody (mAb) into recipient mice resulted in a significant prolongation of graft survival (mean graft survival was 29.2 days). Moreover, anti-L3T4 mAb treatment plus thymectomy led to indefinite graft survival. Anti-rat endothelial cell (EC) antibody production in the grafted mice was remarkably suppressed by anti-L3T4 mAb treatment. In contrast, Lyt2.1 mAb treatment did not prolong the graft survival and did not suppress anti-EC antibody production. These results indicated the absolute requirement of L3T4+ T cells in the rejection of rat to mouse cardiac xenografts.
First Department of Surgery, Osaka University Medical School, Suita, Japan.
G
G
Matsumiya
R
R
Shirakura
S
S
Miyagawa
H
H
Izutani
S
S
Nakata
Y
Y
Shimazaki
S
S
Nakano
H
H
Matsuda
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D007376:Interleukin-2 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013934:Thymectomy; D014183:Transplantation, Heterologous / Q000276:immunology*; D014185:Transplantation, Isogeneic / Q000276:immunology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2