T cell stimulation in vivo by lipopolysaccharide (LPS)

Abstract

Lipopolysaccharide (LPS) from gram-negative bacteria causes polyclonal activation of B cells and stimulation of macrophages and other APC. We show here that, under in vivo conditions, LPS also induces strong stimulation oft cells. As manifested by CD69 upregulation, LPS injection stimulates both CD4 and CD8+ T cells, and, at high doses, stimulates naive (CD44(lo)) cells as well as memory (CD44(hi)) cells. However, in terms of cell division, the response of T cells after LPS injection is limited to the CD44(hi) subset of CD8+ cells. In contrast with B cells, proliferative responses of CD44(hi) CD8+ cells require only very low doses of LPS (10 ng). Based on studies with LPS-nonresponder and gene-knockout mice, LPS-induced proliferation of CD44(hi) CD8+ cells appears to operate via an indirect pathway revolving LPS stimulation of APC and release of type I (α, α) interferon (IFN-I). Similar selective stimulation of CD44(hi) CD8+ cells occurs in viral infections and after injection of IFN-I, implying a common mechanism. Hence, intermittent exposure to pathogens (gram-negative bacteria and viruses) could contribute to the high background proliferation of memory-phenotype CD8+ cells found in normal animals.