Effect of IL-4 deletion on cardiac allograft survival in the BALB/c to 129SvxC57BL/6 strain combination

To investigate the effect of IL-4 deletion on cardiac allograft survival, v ascularized BALB/c cardiac allografts were placed in C57BL/6, 129SvxC57BL/6 (IL-4 +/+) or 129SvxC57BL/6 IL-4 knockout mice (IL-4-/-). Untreated recipi ents rejected allografts in < 15 days while isografts survived indefinitely (> 100 days). Treatment with anti-CD4 (GK1.5) for 4 days at the time of al lografting increased mean survival to > 100 days in C57BL/6, 90 +/- 16 days in 129SvxC57BL/6 (IL-4 +/+) and 68 +/- 36 days in 129SvxC57BL/6 (IL-4-/-) recipients. Although there was a trend towards shorter survival times in th e IL-4-/- mAb-treated mice, survival in the three recipient groups was not significantly different (P = 0.07). A 30-day course of anti-CD4 did not fur ther prolong BALB/c heart survival. All long-surviving hearts had histologi cal evidence of parenchymal damage and transplant vascular disease. None of these recipients developed antigen-specific tolerance, since both donor an d third party skin graft challenges were rejected when challenged at > 60 d ays post-graft and all primary grafts failed by 120 days. Thus the effects of IL-4 deletion were subtle and were seen only with low doses of immunosup pression in this high responder strain combination.