Stimulation of Human T Lymphocytes by LPS Is MHC Unrestricted, But Strongly Dependent on B7 Interactions

Recently, we have shown that LPS is a potent inducer of human T cell proliferation and lymphokine production. However, the activation of T cells by LPS has been demonstrated to be monocyte dependent and to require direct cell-to-cell contact. Here, we investigated the role of monocytes as accessory cells and the requirement for costimulatory signals in more detail. We found that the accessory cell activity of monocytes during LPS-induced T cell proliferation is characterized by the following features: LPS-primed monocytes are competent stimulators of T cell proliferation; interaction of LPS with monocytes during the priming step is dependent on CD14 and is sensitive to ammonia; monocyte/T cell interactions are not MHC restricted but are strongly dependent on interactions of CD28 and/or CTLA-4 on T cells and their ligands CD80 and/or CD86 on monocytes. CD80 seems to be crucial for the activation of T cells by monocytes, since monocytes expressing CD86 but not CD80 after LPS stimulation were unable to stimulate T cells; IL-12, at least as a costimulatory factor, but not IL-15, is important in LPS-induced T cell proliferation. Taken together, our results indicate that LPS acts neither as a mitogen, nor as a superantigen, nor as an Ag. The activation of human T cells by LPS requires the help of accessory functions by primed monocytes and is MHC unrestricted but needs costimulatory signals via CD28 and/or CTLA-4.