Selective loss of natural killer T cells by apoptosis following infection with lymphocytic choriomeningitis virus

Natural killer T (NKT) cells, a unique subpopulation of T cells, coexpress markers also present on NK cells and recognize the major histocompatibility complex class I-like CD1d1 molecule. We studied the effect of an acute vir us infection on NKT cells. Mice were infected with the nonhepatotropic Arms trong strain of lymphocytic choriomeningitis virus (LCMV) and at various ti mes postinfection, mononuclear cells from the liver, peritoneum, and spleen were isolated. It was found that within 2 to 3 days, there was a selective loss of NKT cells from the liver with an apparent rapid recovery within 8 to 14 days. There was no increase in peritoneal or splenic NKT cells, indic ating that NKT cells did not traffic to these tissues. This loss of NKT cel ls was independent of gamma interferon (IFN-gamma) and interleukin 12 (IL-1 2) production, but did occur in mice treated,,vith poly(I-C), a classical i nducer of IFN-alpha/beta. The reduction in NKT cells was CD28 and fas/fasL independent and occurred via apoptosis. It was not observed in LCMV-infecte d DNA fragmentation factor 45-deficient mice, and an increase in active cas pase 3-specific staining was found in liver NKT cells from LCMV-infected an d poly(I-C)-treated mice compared to uninfected wild-type mice. Interesting ly, it was also found that liver NKT cells from LCMV-infected mice were the mselves infected. These results suggest that the loss of NKT cells followin g an acute LCMV infection could be due to the induction of IFN-alpha/beta r esulting in NKT-cell apoptosis and is important for the host's immune respo nse to LCMV.