Endotoxin and lipid A stimulate proliferation of human T cells in the presence 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 and requires 100 to 10,000 ng/ml of LPS or synthetic lipid A (compound 506) for optimal stimulation. In contrast, the synthetic lipid A precursor Ia (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 lymphocyte preparations with less than 0.1% monocytes are not stimulated by LPS, showing that monocytes are required for T cell proliferation. Reconstitution experiments show that only monocytes, but not B lymphocytes, are able to support induction of DNA synthesis. Separating LPS-stimulated monocytes from T lymphocytes by a membrane, permeable for cytokines but not for cells, abolishes T cell proliferation. Fixation of monocytes 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 proliferation in the absence of additional LPS. Our results indicate that human T cells respond in a monocyte-supported manner to LPS exposure by proliferation and lymphokine production. We hypothesize that this reactivity of T lymphocytes to LPS may be of clinical relevance.
Mattern
T
T
Borstel Research Institute, Germany.
Thanhäuser
A
A
Reiling
N
N
Toellner
K M
KM
Duchrow
M
M
Kusumoto
S
S
Rietschel
E T
ET
Ernst
M
M
Brade
H
H
Flad
H D
HD
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D008050:Lipid A / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D017931:DNA Primers; D008050:Lipid A; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2