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J. Exp. Med.,
Volume 187, Number 2, January 19, 1998 225-236
By

From the * Department of Microbiology and the Center for Immunology, University of Minnesota,
Minneapolis, Minnesota 55455; and The adoptive transfer of naive CD4+ T cell receptor (TCR) transgenic T cells was used to investigate the mechanisms by which the adjuvant lipopolysaccharide (LPS) enhance T cell clonal
expansion in vivo. Subcutaneous administration of soluble antigen (Ag) resulted in rapid and
transient accumulation of the Ag-specific T cells in the draining lymph nodes (LNs), which was
preceded by the production of interleukin (IL)-2. CD28-deficient, Ag-specific T cells produced only small amounts of IL-2 in response to soluble Ag and did not accumulate in the LN
to the same extent as wild-type T cells. Injection of Ag and LPS, a natural immunological adjuvant, enhanced IL-2 production and LN accumulation of wild-type, Ag-specific T cells but
had no significant effect on CD28-deficient, Ag-specific T cells. Therefore, CD28 is critical for
Ag-driven IL-2 production and T cell proliferation in vivo, and is essential for the LPS-mediated enhancement of these events. However, enhancement of IL-2 production could not explain the LPS-dependent increase of T cell accumulation because IL-2-deficient, Ag-specific T
cells accumulated to a greater extent in the LN than wild-type T cells in response to Ag plus LPS. These results indicate that adjuvants improve T cell proliferation in vivo via a CD28-dependent signal that can operate in the absence of IL-2.
the Department of Medicine and Committee on Immunology,
University of Chicago, Chicago, Illinois 60637
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