asialo-gm1-ganglioside and Hepatitis--Viral--Animal

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

The eradication of infectious virus from the central nervous system (CNS) following infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) is thought to be immune-mediated. Furthermore, a significant decrease of infectious virus coincides with the appearance of prominent inflammatory infiltrates in the brain and spinal cord. In the present study, mononuclear cells infiltrating the brain during JHMV infection were isolated and characterized. While all subsets of immune cells were present, there appeared to be a temporal relationship between the peak incidence of CD8+ T cells (40% of total isolated cells) and reduction of virus at day 7 post-infection. Cells with the natural killer (NK) phenotype (at least 30%) were also present throughout infection. These data suggest that CD8+ T cells and NK cells are prominent among cells which infiltrate the brain during JHM virus infection and may have important roles in reduction of virus within the CNS.

Topics: Animals; Brain; G(M1) Ganglioside; Glycosphingolipids; Hepatitis, Viral, Animal; Killer Cells, Natural; Leukocytes, Mononuclear; Lymphocytes; Mice; Mice, Inbred BALB C; Murine hepatitis virus; Phenotype; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory