INDUCTION OF BYSTANDER T-CELL PROLIFERATION BY VIRUSES AND TYPE-I INTERFERON IN-VIVO

T cell proliferation in vivo is presumed to reflect a T cell receptor (TCR)-mediated polyclonal response directed to various environmental a ntigens, However, the massive proliferation of T cells seen in viral i nfections is suggestive of a bystander reaction driven by cytokines in stead of the TCR. In mice, T cell proliferation in viral infections pr eferentially affected the CD44(hi) subset of CD8(+) cells and was mimi cked by injection of polyinosinic-polycytidylic acid [poly(I:C)], an i nducer of type I interferon (IFN I), and also by purified IFN I; such proliferation was not associated with up-regulation of CD69 or CD25 ex pression, which implies that TCR signaling was not involved, IFN I [po ly(I:C)]-stimulated CD8(+) cells survived for prolonged periods in viv o and displayed the same phenotype as did long-lived antigen-specific CD8(+) cells, IFN I also potentiated the clonal expansion and survival of CD8(+) cells responding to specific antigen, Production of IFN I m ay thus play an important role in the generation and maintenance of sp ecific memory.