Induction of proliferation and cytokine production in human T lymphocytes by lipopolysaccharide (LPS).
Lipopolysaccharide (LPS), also known as endotoxin, is a compound of the cell wall of Gram-negative bacteria, which has been demonstrated to induce inflammatory 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 even B lymphocytes. We have now established that T lymphocytes could also contribute to an inflammatory reaction to LPS. LPS is a potent inducer of human T-lymphocyte proliferation and cytokine production. The activation of T lymphocytes by LPS requires direct cell-to-cell contact with viable accessory monocytes. This interaction was found to be MHC-unrestricted, but strongly 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 cells, which circulate in peripheral blood in very low frequency, exert essential 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 observation that depletion of CD34-positive blood stem cells resulted in a complete loss of LPS-induced T-lymphocyte stimulation. Addition of CD34-enriched 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. Furthermore, the involvement of hematopoietic blood stem cells in the activation of T lymphocytes by LPS demonstrates a role of these cells in inflammatory and immunological events.
Ulmer
A J
AJ
Department of Immunology and Cell Biology, Division of Cellular Immunology, Research Center Borstel, Parkallee 22, 23845, Borstel, Germany. ajulmer@fz-borstel.de
Flad
H
H
Rietschel
T
T
Mattern
T
T
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects*
D016207:Cytokines; D008070:Lipopolysaccharides