asialo-gm1-ganglioside and Adenoviridae-Infections

Viral infection of the liver causes accumulation of T cells in the infected organ, raising the question as to the signals that mediate this response. Employing an adenovirus induced hepatitis model in mice, we show that IP-10 and Mig are essential for T cell recruitment and that induction of the two chemokines occurs concomitant to production of IFNgamma. It is shown that while IFNgamma induces IP-10 and Mig in hepatocytes, for optimal chemokine induction, a co-stimulatory signal mediated by cross-linking of Fas on hepatocytes is required. Moreover, cross-linking of Fas by injection of anti-Fas antibody into mice triggers induction of IP-10 and Mig in the liver. The cells providing the two signals are shown to express NK1.1 and AsGM1; elimination of these cells leads to inhibition of IFNgamma and chemokine transcript induction. The conclusion is drawn that both NK cells and T cells provide the two signals for induction of IP-10 and Mig in the liver.

Topics: Adenoviridae Infections; Animals; Antibodies; Antigens; Antigens, Ly; Antigens, Surface; Cell Line; Chemokine CXCL10; Chemokine CXCL9; Chemokines, CXC; Disease Models, Animal; fas Receptor; Female; G(M1) Ganglioside; Hepatitis, Viral, Animal; Intercellular Signaling Peptides and Proteins; Interferon-gamma; Killer Cells, Natural; Lectins, C-Type; Liver; Lymphocyte Subsets; Mice; Mice, Inbred C57BL; Mice, SCID; NK Cell Lectin-Like Receptor Subfamily B; Proteins; Signal Transduction; T-Lymphocytes; Up-Regulation

NK cells are a relatively rare cell population in peripheral lymphoid organs but are abundant in the liver, raising questions as to their function in immune responses to infections of this organ. To investigate this, cell-mediated immunity to viral liver infection induced by a type 5, replication-defective, adenovirus was examined. It is shown that NK cells in the absence of T cells cause hepatocyte apoptosis in virus-infected livers associated with an increase in liver enzymes in the serum. Concomitantly, NK cells induce production of IFN-gamma, inhibitable by their elimination before infection. NK cells are shown to be necessary for optimal priming of virus-specific T cells, assessed by delayed-type hypersensitivity response and CTL activity, consistent with their ability to secrete IFN-gamma. The conclusion is drawn that NK cells mediate two important functions in the liver: they induce cell death in the infected organ and concomitantly stimulate the induction of T cell-mediated immunity by release of IFN-gamma.

Topics: Adenoviridae Infections; Animals; Antigens; Antigens, Surface; Female; G(M1) Ganglioside; Hepatitis, Animal; Interferon-gamma; Killer Cells, Natural; Lectins, C-Type; Lymphocyte Activation; Lymphocyte Depletion; Mice; Mice, Inbred C57BL; Mice, Nude; Mice, SCID; NK Cell Lectin-Like Receptor Subfamily B; Protein Biosynthesis; Proteins; T-Lymphocyte Subsets