Abstract
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.
Original language | English |
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Pages (from-to) | 2996-3004 |
Number of pages | 9 |
Journal | Journal of Immunology |
Volume | 153 |
Issue number | 7 |
Publication status | Published - 1 Oct 1994 |
Keywords
- Humans
- Gene Expression
- Receptors, Interleukin-2
- CD4-Positive T-Lymphocytes
- RNA, Messenger
- Lymphocyte Activation
- Base Sequence
- Adult
- DNA Primers
- Molecular Sequence Data
- Immunologic Memory
- Cytokines
- Lipopolysaccharides
- Lipid A
- Middle Aged
- Monocytes
- Antigen-Presenting Cells
- T-Lymphocyte Subsets