Disturbed MHC regulation in the IFN-gamma knockout mouse. Evidence for three states of MHC expression with distinct roles for IFN-gamma.
We compared the expression of MHC class I and II products in tissues of IFN-gamma knockout (GKO) vs normal (wild-type) BALB/c mice. We studied expression in the basal state, after local tissue injury, after stimuli that induce systemic MHC expression (allogeneic cells, oxazolone skin painting, or LPS), and after rIFN-gamma. Basal class II expression in interstitial cells was not reduced in GKO mice. However, GKO mice had less basal class I expression in kidney, liver, heart, and arterial endothelium than wild-type mice. Local renal ischemic injury increased class I and II expression in kidney tubules of both GKO and wild-type mice, but induction in GKO was less than in wild-type. Potent inflammatory stimuli increased systemic MHC class I and II markedly in kidney, liver, and heart of wild-type mice, but induced no increase in GKO mice. rIFN-gamma induced class I and II equally in GKO and wild-type mice. Thus, three states of MHC expression can be defined that differ in their dependencies on IFN-gamma: basal, locally induced, and systemically induced. Basal class II expression in interstitial cells is IFN-gamma independent, but basal class I expression, particularly in arterial endothelium, is partially dependent on IFN-gamma. The local increase in MHC class I and II in parenchymal cells in response to injury reflects both IFN-gamma and a non-IFN-gamma factor. Systemic MHC class I and II induction is almost exclusively due to IFN-gamma.
Goes
N
N
Department of Medicine, University of Alberta, Edmonton, Canada.
Sims
T
T
Urmson
J
J
Vincent
D
D
Ramassar
V
V
Halloran
P F
PF
D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000172:deficiency*; D007511:Ischemia / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma