Rejection of cardiac xenografts by CD4(+) or CD8(+) T cells

We recently showed that brief complement inhibition induces accommodation o f hamster cardiac transplants in nude rats. We have reconstituted nude rats carrying an accommodated xenograft with syngeneic CD4(+) or CD8(+) T cells to investigate the cellular mechanism of xenograft rejection. We show that CD4(+) T cells can initiate xenograft rejection (10 +/- 1.7 days) by promo ting production of IgG xenoreactive Abs (XAb). These XAb are able to activa te complement as well as to mediate Ab-dependent cell-mediated cytotoxicity . Adoptive transfer of these XAb into naive nude rats provoked hyperacute x enograft rejection (38 +/- 13 min), The rejection was significantly (p < 0. 001) delayed by cobra venom factor (CVF; 11 +/- 8 h in four of five cases) but was still more rapid than in control nude rats (3.3 +/- 0.5 days). CVF plus NK cell depletion further prolonged survival (>7 days in four of five cases; p < 0.01 vs CVF only). CD8(+) T cell-reconstituted nude rats rejecte d their grafts later (19.4 +/- 5.8 days) and required a larger number of ce lls for transfer as compared with CD4(+) T cell-reconstituted nude rats. Ho wever, second xenografts were rejected more rapidly than first xenografts i n CD8(+) T cell-reconstituted nude rats (9 +/- 2 days), indicating that the CD8(+) T cells had been activated. This study demonstrates that CD4(+) and CD8(+) T cells can both reject xenografts. The CD4(+) cells do so at least in part by generation of helper-dependent XAb that act by both complement- dependent and Ab-dependent cell-mediated cytotoxicity mechanisms; the CD8() cells do so as helper-independent cytotoxic T cells.