IP-10 and Mig facilitate accumulation of T cells in the virus-infected liver.
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.
Arai
Katsumitsu
K
Department of Molecular Microbiology and Immunology, USC/Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA.
Liu
Zhang Xu
ZX
Lane
Thomas
T
Dennert
Gunther
G
D000257:Adenoviridae Infections / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000941:Antigens / Q000032:analysis; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000032:analysis; D002460:Cell Line; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005677:G(M1) Ganglioside / Q000032:analysis; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D008099:Liver / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000032:analysis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D019014:fas Receptor / Q000096:biosynthesis / Q000494:pharmacology
D000906:Antibodies; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D019014:fas Receptor; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma