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.
Department of Pathology, Winship Cancer Center, Emory University School of Medicine, Atlanta, Ga 30322.
K W
KW
Sell
K
K
Kanter
G E
GE
Rodey
Y C
YC
Wang
A A
AA
Ansari
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