ENDOTOXIN AND LIPID-A STIMULATE PROLIFERATION OF HUMAN T-CELLS IN THEPRESENCE OF AUTOLOGOUS MONOCYTES

In this paper we describe a new activity of LPS and partial structures : the induction of DNA synthesis and lymphokine production of human T lymphocytes. The LPS-induced T cell proliferation is dose dependent an d requires 100 to 10,000 ng/ml of LPS or synthetic lipid A (compound 5 06) for optimal stimulation. In contrast, the synthetic lipid A precur sor la (compound 406) is not active but rather antagonizes LPS-induced proliferation. The proliferation is accompanied by the expression of mRNA for the Th1 cell-derived lymphokines IFN-gamma and IL-2, but not for the Th2 lymphokines IL-4, IL-5, or IL-10. Highly enriched T lympho cyte preparations with less than 0.1% monocytes are not stimulated by LPS, showing that monocytes are required for T cell proliferation. Rec onstitution experiments show that only monocytes, but not B lymphocyte s, are able to support induction of DNA synthesis. Separating LPS-stim ulated monocytes from T lymphocytes by a membrane, permeable for cytok ines but not for cells, abolishes T cell proliferation. Fixation of mo nocytes with paraformaldehyde also abrogates their accessory function for T cells. If the monocytes are preincubated for 2 h at 37 degrees C with LPS and then washed, they still are able to induce T cell prolif eration in the absence of additional LPS. Our results indicate that hu man T cells respond in a monocyte-supported manner to FPS exposure by proliferation and lymphokine production. We hypothesize that this reac tivity of T lymphocytes to LPS may be of clinical relevance.