Acute rejection of vascularized heart allografts in the absence of IFNgamma.
It is generally assumed that IFNgamma plays a central role in acute allograft rejection. To test this hypothesis, we transplanted fully allogeneic (MHC class I and II incompatible) C3H/HeJ (H2k) murine hearts to IFNgamma-/- (IFNgamma gene-knockout) and IFNgamma+/+ BALB/c (H2d) mice. The phenotype of IFNgamma-/- mice was confirmed by demonstrating absent IFNgamma protein production by Con A stimulated IFNgamma-/- splenocytes. Both IFNgamma-/- and IFNgamma+/+ strains rejected transplanted hearts acutely: graft survival (mean +/- SD) was 5.2+/-0.4 and 6.0+/-0.0 days, respectively. Histologic examination revealed similar patterns of acute cellular rejection in both mouse groups. IFNgamma mRNA was present in hearts rejected by IFNgamma+/+ mice but was absent in those rejected by IFNgamma-/- mice. IL-2, IL-4, IL-10, and TNFalpha mRNA expression, on the other hand, was similar in grafts rejected by either strain. We also observed that hapten-induced delayed-type hypersensitivity (DTH) response was significantly reduced but not absent in IFNgamma-/- mice. Our results demonstrate that IFNgamma is not required for acute cellular rejection of fully allogeneic murine hearts. We propose that non-DTH mechanisms of allograft destruction could be enhanced in the absence of IFNgamma and thus lead to robust acute rejection.
Saleem
S
S
Renal Division, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, Georgia 30033, USA.
Konieczny
B T
BT
Lowry
R P
RP
Baddoura
F K
FK
Lakkis
F G
FG
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics / Q000517:prevention & control; D006241:Haptens / Q000009:adverse effects; D016027:Heart Transplantation / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000209:etiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000032:analysis
D000276:Adjuvants, Immunologic; D016207:Cytokines; D006241:Haptens; D012333:RNA, Messenger; D007371:Interferon-gamma