Evidence that rat renal allografts are rejected by cytotoxic T cells and not by nonspecific effectors.

Infiltrating cells were harvested on day 5 from rat renal allografts (LEW X BN into LEW) that were either rejecting (untreated) or healthy (cyclosporine [CsA]-treated or passively enhanced with LEW anti-BN serum). Similar numbers of cells were harvested from rejecting (mean 11 X 10(7), range 8-15 X 10(7], CsA-treated (6 X 10(7), 5-7 X 10(7], and enhanced (9 X 10(7), 7-10 X 10(7] grafts. These cells were a heterogeneous population of mononuclear cells. Fluorescence-activated cells sorter analysis after labeling with a range of monoclonal antibodies showed that they all labeled with MRC OX-1 (against the leukocyte-common antigen), and that about one-third of infiltrating cells bound MRC OX-19 (pan-T cells) and one-third bound MRC OX-12 (B cells), with little difference between the rejecting, CsA-treated or enhanced grafts. However, the ratio of the numbers of W3/25-positive cells (helper T cells and macrophages) to MRC OX8-positive cells (cytotoxic T cells and natural killer cells) was less in untreated (mean 0.6, range 0.5-0.6) than in CsA-treated (1.3, 0.8-1.6) or enhanced (2.1, 1.8-2.4) grafts. Using a 6-hr chromium-release assay, cells from untreated, CsA-treated, and enhanced grafts showed similar levels of nonspecific cytotoxicity (against Y3 myeloma cells), but only untreated grafts showed alloantigen-specific target cell lysis (against BN concanavalin A blasts). These results suggest that specific cytotoxic T cells rather than nonspecific responses play an essential role in allograft rejection in the rat.