EARLY EXPRESSION OF INTERFERON-?? INDUCIBLE PROTEIN 10 AND MONOKINE INDUCED BY INTERFERON-?? IN CARDIAC ALLOGRAFTS IS MEDIATED BY CD8+ T CELLS1

Abstract

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-γ inducible protein 10 (IP-10) and monokine induced by IFN-γ, (Mig), in allogeneic heart grafts. Methods. Syngeneic or allogeneic A/J (H-2^a) hearts were heterotopically transplanted to wild-type, CD4^\-/\-, CD8α^\-/\-, or IFN-γ^\-/\- C57BL/6 (H-2^b) recipients. To test expression of IP-10 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-NK 1.1, anti-CD4, and/or anti-CD8 monoclonal antibodies before transplantation. Results. Allogeneic heart grafts transplanted to wild-type, but not IFN-γ^\-/\-, 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.