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Lipopolysaccharide enhances in vivo interleukin‐2 production and proliferation by naive antigen‐specific CD4 T cells via a Toll‐like receptor 4‐dependent mechanism

Microbial adjuvants are essential for the development of T‐cell‐dependent antibody production, recall T‐cell proliferation and interferon‐γ production following immunization with protein antigens. Using an adoptive transfer approach, we showed that the adjuvant lipopolysaccharide enhanced the frequency of cells producing interleukin‐2, enhanced clonal expansion by antigen‐specific CD4 T cells and increased CD86 and interleukin‐1α production by antigen‐presenting cells. All of these effects were dependent on Toll‐like receptor‐4 (TLR4) expression by cells other than the antigen‐specific CD4 T cells. The ability of lipopolysaccharides to increase the number of antigen‐specific CD4 T cells that survive after immunization probably explains the previous finding that antigen‐specific proliferation by T cells from normal mice depends on previous exposure to antigen and adjuvant.