CARDIAC ALLOGRAFTS FROM IL-4 KNOCKOUT RECIPIENTS - ASSESSMENT OF TRANSPLANT ARTERIOSCLEROSIS AND PERIPHERAL TOLERANCE

To study the role of IL-4 in tolerance induction and transplant arteri osclerosis, BALB/c hearts were transplanted into C57BL/6J wild-type or IL-4 knockout (IL-4(-/-)) recipients. A 30-day course of anti-CD4/8 m Ab was used to induce long term graft survival. Primary graft survival was 50% (5 of 10) in IL-4(-/-) recipients comparable to 63% (5 of 8) in wild-type recipients. Mice with allografts surviving >80 days were tested for tolerance by challenge with a second donor or third partly (CBA) heart, Secondary donor-strain heart grafts survived >30 days, hu t showed histologic evidence of ongoing alloimmune response. Third par ty hearts rejected rapidly. Although immunostaining and P-32 BT-PCR as says showed no differences in the mononuclear cell infiltration and T cell activation between LL-4(-/-) and wild-type tolerant recipients, s ome monokines (IL-12, TNF-alpha, and allograft inflammatory factor-1) were up-regulated in grafts from IL-4-/- recipients. Computer-assisted analysis of elastin-stained vessels revealed that the severity of vas cular thickening (percentage of luminal occlusion, mean +/- SD, n = 32 9) was similar in grafts from IL-4(-/-) (63.7 +/- 16.9%) and wild-type (69.5 +/- 17.6%) recipients. Thus, IL-4 deficiency did not alter prim ary or secondary graft survival, infiltration, or vascular thickening, The selective alterations in monokine expression suggests that altern ative pathways are activated and may compensate in IL-4(-/-) mice.