Widespread and selective induction of major histocompatibility complex-determined antigens in vivo by gamma interferon.

Abstract

gamma Interferon (IFN-gamma) caused remarkable increases in class I (H-2Kk) and class II (I-Ak) antigens throughout the body by 6-9 d. Heart, kidney, and adrenals showed increases of 4-8 times their previous levels of class I antigen content, while the pancreas and small intestine increased 13-17-fold. Lesser increases were found in spleen, liver, and lung, which showed higher resting antigenic potency. Increases of class II antigenicity of 6-10-fold were found in heart, kidney, pancreas, lung, liver, adrenal, and small intestine, with lesser increases in thymus and spleen, and none in lymph node. Topographical analysis revealed that IFN-gamma induced class I and II antigens on most tissues in a highly selective fashion. For example, the renal proximal tubules expressed large amounts of both class I and II antigens, whereas the distal tubules and collecting ducts did not. In some epithelial cells class I and II determinants were induced only on the basal aspects of the cell membrane. IFN-gamma caused a remarkable increase in class II-positive dendritic cells in the liver, pancreas, salivary glands, and thyroid. Whether these cells were of local or systemic origin is uncertain, but the finding of a simultaneous depletion of dendritic cells from lymph nodes and spleen raises the possibility that they may have been derived, at least in part, from these sites. The dynamic and selective induction of class I and II antigen expression by IFN-gamma is likely to be important in regulation of the immune response in tissues.

Liver NK cells expressing TRAIL are toxic against self hepatocytes in mice

“…It has been thought that the expression of MHC class I molecules on hepatocytes is almost undetectable but is up-regulated by IFN-␥. 13 In conflict with such an accepted belief, the significant expression of MHC class I molecules was detected on freshly isolated murine hepatocytes by FCM (Fig. 7B).…”

“…In general, the presence of self-major histocompatibility complex (MHC) class I molecules protects target cells from lysis mediated by NK cells via binding to inhibitory recep-tors. 1,11,12 Although it is not clear at present how liver NK cells kill self-hepatocytes, it has been speculated that hepatocytes do not express sufficient MHC class I to inhibit NK cell-induced killing 13 or that liver NK cells include a cell population lacking sufficient inhibitory receptors. Another possibility is that liver NK cells include a cell population expressing certain effector molecules that cannot be downregulated even by self-class I recognition via NK inhibitory receptors.…”

Cellular mRNA expression of interferon-gamma, IL-4 and transforming growth factor-beta (TGF-β) by rat mononuclear cells stimulated with peripheral nerve myelin antigens in experimental allergic neuritis

“…in autoimmune diseases. Interferon-gamma (IFN-7) is a putative disease up-regulator, as it induces MHC antigens [15], activation of macrophages [16] and leads to induction of T cell homing [17]. IFN-7 secretion at the target site for autoaggressive immunity has been implicated in the pathogenesis of the tissue damage in experimental allergic encephalomyelitis (EAE) and EAN [11,18,19].…”

Differential Usage of Class II Transactivator Promoters PI and PIV during Inflammation and Injury in Kidney

“…In addition, in human kidney in the basal state, a variable number of epithelial and endothelial cells express class II (3), perhaps due to basal production of interferon-␥ (IFN-␥) (4). Expression of class II in mouse kidney endothelium and epithelium can be induced de novo by IFN-␥ (5,6).…”