Endotoxin and lipid A stimulate proliferation of human T cells in the presence of autologous monocytes

T Mattern, A Thanhäuser, N Reiling, K M Toellner, M Duchrow, S Kusumoto, E T Rietschel, M Ernst, H Brade, H D Flad

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95 Citations (Scopus)


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 languageEnglish
Pages (from-to)2996-3004
Number of pages9
JournalJournal of Immunology
Issue number7
Publication statusPublished - 1 Oct 1994


  • 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


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