Effect of IL-4 deletion on cardiac allograft survival in the BALB/c to 129Sv x C57BL/6 strain combination.
To investigate the effect of IL-4 deletion on cardiac allograft survival, vascularized BALB/c cardiac allografts were placed in C57BL/6, 129Sv x C57BL/6 (IL-4 +/+) or 129Sv x C57BL/6 IL-4 knockout mice (IL-4-/-). Untreated recipients rejected allografts in < 15 days while isografts survived indefinitely (> 100 days). Treatment with anti-CD4 (GK1.5) for 4 days at the time of allografting increased mean survival to > 100 days in C57BL/6, 90+/-16 days in 129Sv x C57BL/6 (IL-4 +/+) and 68 +/- 36 days in 129Sv x C57BL/6 (IL-4-/-) recipients. Although there was a trend towards shorter survival times in the 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 further prolong BALB/c heart survival. All long-surviving hearts had histological evidence of parenchymal damage and transplant vascular disease. None of these recipients developed antigen-specific tolerance, since both donor and third party skin graft challenges were rejected when challenged at > 60 days 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 immunosuppression in this high responder strain combination.
Mottram
P
P
Department of Surgery, Royal Melbourne Hospital, Parkville, Australia. p.mottram@medicine.unimelb.edu.au
Murray-Segal
L J
LJ
Li
Y Q
YQ
Han
W R
WR
Sandrin
M
M
McKenzie
I F
IF
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D011817:Rabbits; D016038:Skin Transplantation / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015847:Interleukin-4