Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. VI. In vitro alloreactivity of T cell subsets from rats with long-surviving allografts.
DA rats treated with a short course of cyclosporine develop specific unresponsiveness to RT1-incompatible PVG donor heart allografts. CD4+ cells, not CD8+ cells, transfer unresponsiveness to irradiated rats. However, host-derived CD8+ cells are important in reestablishing unresponsiveness. In this study, unfractionated lymphoid cells and W3/25+ (CD4+) cells from CsA-treated rats with long-surviving PVG allografts demonstrated normal alloreactivity to PVG alloantigen in the mixed lymphocyte culture and failed to suppress the proliferative response of naive W3/25+ cells to donor-specific alloantigen. MRC OX8+ (CD8+) cells did not proliferate. Sera from CsA-treated rats had no effect on the MLC reactivity of cells from CsA-treated rats, suggesting that blocking or antiidiotypic antibodies did not diminish alloreactivity. IL-2 production by W3/25+ cells from CsA-treated rats was similar to that by W3/25+ cells from naive rats. Specific cytotoxic T cells to PVG were generated in MLC, and the frequency of precursor cytotoxic lymphocytes in CsA-treated rats was similar to that in naive DA rats. In an in vitro assay testing response to idiotype, neither W3/25+ or MRC OX8+ cells from unresponsive rats proliferated. As CD4+ cells from CsA-treated rats lose their capacity to adoptively transfer specific unresponsiveness unless maintained in a cytokine-rich supernatant, all in vitro assays were performed with and without added cytokines, but no change in reactivity consistent with suppression was observed in any assay. CD4+ suppressor cells had no effect on conventional in vitro assays of alloreactivity, preventing the detection of the unresponsiveness in vitro.
Pearce
N W
NW
Department of Medicine, Stanford University School of Medicine, California 94305.
Berger
M F
MF
Gurley
K E
KE
Spinelli
A
A
Hall
B M
BM
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014184:Transplantation, Homologous
D006649:Histocompatibility Antigens; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2; D007519:Isoantigens; D007371:Interferon-gamma; D016572:Cyclosporine