Characterization of human heart-infiltrating cells after transplantation. V. Suppression of donor-specific allogeneic responses by cloned T-cell lines isolated from heart biopsy specimens of patients after transplantation.
In vitro culture of heart biopsy specimens from patients after transplantation in media containing recombinant human interleukin-2 led to the exudation of host mononuclear-cell infiltrates. Cloned T-cell lines were prepared from such infiltrates and studied for donor-specific mixed lymphocyte reaction and cytotoxic T-lymphocyte activity. Although most T-cell clones (greater than 50%) showed donor-specific reactivity, a small but distinct frequency (2% to 10%) of the cloned T-cell lines did not proliferate against donor or third-party stimulator cells. Of interest was our finding that addition of these non-donor-reactive cloned T-cell lines to autologous peripheral blood mononuclear cells markedly suppressed their donor-specific, but not third-party major histocompatibility complex, unrelated proliferative response and prevented the generation of donor, but not third-party, major histocompatibility complex unrelated cytotoxic T-lymphocyte function. The suppression was not secondary to lysis of donor stimulator cells, lysis of autologous donor-specific CD4+ lymphoblasts, or by selective consumption of interleukin-2. The suppression was mediated at the initiation of sensitization (precursor cell level). These suppressor cells expressed CD3, CD8, CD45RO, and the alpha, beta T-cell receptor, but not CD4 or CD56. These cloned T-cell lines will provide unique reagents to study the molecular basis by which these cells exert their regulatory function.
Sell
K W
KW
Department of Pathology, Winship Cancer Center, Emory University School of Medicine, Atlanta, Ga 30322.
Kanter
K
K
Rodey
G E
GE
Wang
Y C
YC
Ansari
A A
AA
D015703:Antigens, CD / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D007376:Interleukin-2