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.