Skip NavigationSkip to Content
Return Return to Search Results

Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo

  1. Author:
    Abe, K.
    Yarovinsky, F. O.
    Murakami, T.
    Shakhov, A. N.
    Tumanov, A. V.
    Ito, D.
    Drutskaya, L. N.
    Pfeffer, K.
    Kuprash, D. V.
    Komschlies, K. L.
    Nedospasov, S. A.

  2. Author Address

    NCI, SAIC Frederick, Basic Res Program, Ctr Canc Res,Lab Mol Immunoregulat, Bldg 560,Room 31-70, Ft Detrick, MD 21702 USA NCI, SAIC Frederick, Basic Res Program, Ctr Canc Res,Lab Mol Immunoregulat, Ft Detrick, MD 21702 USA NCI, SAIC Frederick, Ctr Canc Res, Expt Immunol Lab, Ft Detrick, MD 21702 USA NCI, SAIC Frederick, Baic Res Program, Ft Detrick, MD 21702 USA Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-8000 Munich, Germany Nedospasov SA NCI, SAIC Frederick, Basic Res Program, Ctr Canc Res,Lab Mol Immunoregulat, Bldg 560,Room 31-70, Ft Detrick, MD 21702 USA
    1. Year: 2003
  2. Journal: Blood
    1. 101
    2. 4
    3. Pages: 1477-1483
  4. Type of Article: Article
  1. Abstract:

    TNF/LTalpha/LTbeta (tumor necrosis factor/lymphotoxin- alpha/lymphotoxin-beta) triple knockout (KO) mice show a significant reduction of dendritic cell (DC) number in the spleen, presumably due to defective recruitment and/or production. To distinguish between these possibilities, DCs were generated from bone marrow (BM) cultures prepared from wild-type (wt) and mutant mice in the presence of granulocyte- macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield of CD11c(+) major histocompatibility complex (MHC) class II+ DCs generated from TNF/LTalpha/LTP-/- BM culture was significantly reduced compared with wt BM culture. In order to further dissect the individual pathways responsible for defective DC properties observed in TNF/LTalpha/LTP-/- mice, the panel of TNF/LT ligand and receptor single KO mice were used. the production of DCs from BM culture was significantly reduced in TNF-/- arid. TNF receptor (TNFR) p55(- /-) mice, but normal in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice. Recombinant TNF (rTNF) exogenously added to TNF/LTalpha/LTbeta(-/-) BM cultures could reverse this defect, and blocking antibodies showed partial effect on BFA cultures of wt mice. Conversely, numbers of mature DCs in spleen were significantly decreased in LTalpha(-/-), LTbeta(-/-), LTbetaR(- /-) mice, but not in TNF-/- and TNFRp55(-/-) mice. These results reveal 2 distinct contributions of fkF/LT cytokines. First, TNF acting through TNF receptor is involved in the development/ maturation of DCs in BM progenitor cultures, but this function appears to be redundant in vivo. Second, the microenvironment in peripheral lymphoid organs associated with LTalpha/LTbeta-LTbetaR Signaling and chemokine production is critical for recruitment efficiency of DCs, and this pathway is indispensable. (C) 2003 by The American Society of Hematology.

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel