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

Background. Our goal was to test the intragraft mRNA expression and production 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 transplanted 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 removed 1-8 days posttransplant for RNA isolation and Northern blot analysis. To test the potential recipient leukocyte populations mediating intraallograft 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-gamma(-/-), recipients expressed IP-10 and Mig at day +2 posttransplant that increased 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 low to undetectable expression of IP-10 and Mig on day +2 posttransplant, Similarly, cardiac allografts from CD8(-/-), but not CD4(-/-) recipients had low to undetectable expression of IP-10 and Mig on day +2 posttransplant. Conclusions. Early intraallograft expression of Mig and IP-10 during primary rejection of cardiac allografts is dependent on the activities of recipient CD8+ T cells.