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.