Induction of proliferation and cytokine production in human T lymphocytes by lipopolysaccharide (LPS)

Lipopolysaccharide (LPS), also known as endotoxin, is a compound of the cel l wall of Gram-negative bacteria, which has been demonstrated to induce inf lammatory reactions in vitro as well as in vivo, including lethal shock. A great number of different cells have been documented to be reactive to LPS, e.g. monocytes/macrophages, Vascular cells, polymorphonuclear cells, and e ven B lymphocytes. We have now established that T lymphocytes could also co ntribute to an inflammatory reaction to LPS. LPS is a potent inducer of hum an T-lymphocyte proliferation and cytokine production. The activation of T lymphocytes by LPS requires direct cell-to-cell contact with viable accesso ry monocytes. This interaction was found to be MHC-unrestricted, but strong ly dependent on costimulatory signals provided by B7/CD28 interactions. The frequency of responding T lymphocytes is less than 1:1000. A very exciting finding was that not only monocytes, but also CD34+ hematopoietic stem cel ls, which circulate in peripheral blood in very low frequency, exert essent ial accessory cell activity during stimulation of T lymphocytes by LPS. In contrast, the response of T lymphocytes to conventional recall antigens is not controlled by blood stem cells. These conclusions are based on the obse rvation that depletion of CD34-positive blood stem cells resulted in a comp lete loss of LPS-induced T-lymphocyte stimulation. Addition of CD34-enriche d blood stem cells led to a recovery of reactivity of T lymphocyte to LPS. The characteristics of T-lymphocyte activation indicate that LPS is neither active as a mitogen, or as a superantigen, or as a classical antigen, but may activate T lymphocyte through a new, so far undescribed, mechanism. Fur thermore, the involvement of hematopoietic blood stem cells in the activati on of T lymphocytes by LPS demonstrates a role of these cells in inflammato ry and immunological events. (C) 2000 Elsevier Science Ireland Ltd. All rig hts reserved.