© The Rockefeller University Press, 0022-1007/1997/6/2089/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 12, June 16, 1997 2089-2094
T Cell Stimulation In Vivo by Lipopolysaccharide (LPS)
David F. Tough,
Siquan Sun, and
Jonathan Sprent
From the Department of Immunology, The Scripps Research Institute, La Jolla, California 92037
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 of T cells. As manifested by CD69 upregulation, LPS injection stimulates both CD4 and CD8+ T cells, and, at high doses, stimulates naive (CD44lo) cells as well as memory (CD44hi) cells. However, in terms of cell division, the response of T cells after LPS injection is limited to the CD44hi subset of CD8+ cells. In contrast with B cells, proliferative responses of CD44hi 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 CD44hi CD8+ cells appears to operate via an indirect pathway involving LPS stimulation of APC and release of type I (
, β) interferon (IFN-I). Similar selective stimulation of CD44hi 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.
Address correspondence to Jonathan Sprent, Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.
1Abbreviations used in this paper: BrdU, bromodeoxyuridine; IFN-I, type I (
, β) interferon; LCMV, lymphocytic choriomeningitis virus.

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