Acute rejection of vascularized heart allografts in the absence of IFNgamma

Transplantation. 1996 Dec 27;62(12):1908-11. doi: 10.1097/00007890-199612270-00039.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Cytokines / genetics
  • Graft Rejection / genetics
  • Graft Rejection / prevention & control
  • Haptens / adverse effects
  • Heart Transplantation / immunology*
  • Hypersensitivity, Delayed / etiology*
  • Interferon-gamma / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • RNA, Messenger / analysis

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Haptens
  • RNA, Messenger
  • Interferon-gamma