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 arteriosclerosis, 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 mAb 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 party (CBA) heart. Secondary donor-strain heart grafts survived >30 days, but showed histologic evidence of ongoing alloimmune response. Third party hearts rejected rapidly. Although immunostaining and 32P RT-PCR assays showed no differences in the mononuclear cell infiltration and T cell activation between IL-4(-/-) and wild-type tolerant recipients, some 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 vascular thickening (percentage of luminal occlusion, mean +/- SD, n = 329) 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 primary or secondary graft survival, infiltration, or vascular thickening. The selective alterations in monokine expression suggests that alternative pathways are activated and may compensate in IL-4(-/-) mice.
Mottram
P L
PL
University of Melbourne, Department of Surgery, Royal Melbourne Hospital, Victoria, Australia.
Räisänen-Sokolowski
A
A
Glysing-Jensen
T
T
Stein-Oakley
A N
AN
Russell
M E
ME
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D013997:Time Factors; D014184:Transplantation, Homologous
D015847:Interleukin-4