Enterotoxin adjuvants have direct effects on T cells and antigen-presenting cells that result in either interleukin-4-dependent or -independent immune responses

In an in vitro study, Escherichia coli heat-labile toxin (LT) was shown to directly affect activated CD4(+) T cells and support interleukin (IL)-5 pro duction in IL-4-deficient (IL-4(-/-)) mice, whereas cholera toxin (CT) did not. Both LT and CT enhanced B7-2 expression on B cells and macrophages. Th ese effects were not influenced by CD40-CD40 ligand cosignaling. Addition o f LT- or CT-treated antigen-presenting cells to anti-CD3-triggered CD4(+) T cells resulted in the induction of T cell proliferative responses. Further , these responses were inhibited by anti-B7-2 monoclonal antibody. Cocultiv ation of CD4(+) T cells with LT- or CT-treated antigen-presenting cells and anti-CD3 enhanced Th1- and IL-4-mediated Th2-type cytokine production, The results from in vitro studies were supported by in vivo studies in IL-4(-/ -) mice, in which LT induced mucosal IgA responses but CT did not. Thus, al though both LT and CT induce mucosal adjuvant responses via IL-4-dependent Th2-type responses, LT also elicits Th1- and IL-4-independent Th2-type resp onses.