A NATURAL IMMUNOLOGICAL ADJUVANT ENHANCES T-CELL CLONAL EXPANSION THROUGH A CD28-DEPENDENT, INTERLEUKIN (IL)-2-INDEPENDENT MECHANISM

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. Subc utaneous administration of soluble antigen (Ag) resulted in rapid and transient accumulation of the Ag-specific T cells in the draining lymp h nodes (LNs), which was preceded by the production of interleukin (IL )-2. CD28-deficient, Ag-specific T cells produced only small amounts o f IL-2 in response to soluble Ag and did not accumulate in rile LN to the same extent as wild-type T cells. Injection of Ag and LPS, a natur al immunological adjuvant, enhanced IL-2, production and LN accumulati on of wild-type, Ag-specific T cells but had no significant effect on CD's-deficient, Ag-specific T cells. Therefore, CD28 is critical for A g-driven IL-2 production and T cell proliferation in vivo, and is esse ntial For the LPS-mediated enhancement of these events. However, enhan cement of IL-2 production could not explain the LPS-dependent increase of T cell accumulation because IL-2-deficient, Ag-specific T cells ac cumulated to a seater extent in the LN than wild-type T cells in respo nse to Ag plus LPS. These results indicate that adjuvants improve T ce ll proliferation in vivo via a CD28-dependent signal chat can operate in the absence of IL-2.