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

A Natural Immunological Adjuvant Enhances T Cell Clonal Expansion through a CD28-dependent, Interleukin (IL)-2-independent Mechanism

By Alexander Khoruts,^* Anna Mondino,^* Kathryn A. Pape,^* Steven L. Reiner, and Marc K. Jenkins^*

From the ^* Department of Microbiology and the Center for Immunology, University of Minnesota, Minneapolis, Minnesota 55455; and   the Department of Medicine and Committee on Immunology, University of Chicago, Chicago, Illinois 60637

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.

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