Early expression of interferon-gamma inducible protein 10 and monokine induced by interferon-gamma in cardiac allografts is mediated by CD8(+) T cells

Background. Our goal was to test the intragraft mRNA expression and product ion of two chemokines that are potent chemoattractants for antigen-primed T cells, interferon-gamma inducible protein 10 (IP-10) and monokine induced by IFN-gamma, (Mig), in allogeneic heart grafts. Methods. Syngeneic or allogeneic A/J (H-2(a)) hearts were heterotopically t ransplanted to wild-type, CD4(-/-), CD8 alpha(-/-), or IFN-gamma(-/-) C57BL /6 (H-2(b)) recipients. To test expression of IP-IO and Mig, grafts were re moved 1-8 days posttransplant for RNA isolation and Northern blot analysis. To test the potential recipient leukocyte populations mediating intraallog raft expression of IP-10 and Mig, recipients were treated with anti-NE 1.1, anti-CD4, and/or anti-CD8 monoclonal antibodies before transplantation. Results. Allogeneic heart grafts transplanted to wild-type, but not IFN-gam ma(-/-), recipients expressed IP-10 and Mig at day +2 posttransplant that i ncreased thereafter until rejection was completed. Expression of IP-10 and Mig in isografts was low or undetectable. Cardiac allografts from CD8(+) T cell depleted, but not NK cell or CD4(+) T cell depleted, recipients had lo w to undetectable expression of IP-10 and Mig on day +2 posttransplant, Sim ilarly, cardiac allografts from CD8(-/-), but not CD4(-/-) recipients had l ow to undetectable expression of IP-10 and Mig on day +2 posttransplant. Conclusions. Early intraallograft expression of Mig and IP-10 during primar y rejection of cardiac allografts is dependent on the activities of recipie nt CD8+ T cells.