Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2

Tilo Biedermann, Manfred Kneilling, Reinhard Mailhammer, Konrad Maier, Christian A. Sander, George Kollias, Steven L. Kunkel, Lothar Hültner, Martin Röcken

Research output: Contribution to journalArticlepeer-review

356 Scopus citations

Abstract

Polymorphonuclear leukocytes (PMNs) characterize the pathology of T cell-mediated autoimmune diseases and delayed-type hypersensitivity reactions (DTHRs) in the skin, joints, and gut, but are absent in T cell-mediated autoimmune diseases of the brain or pancreas. All of these reactions are mediated by interferon γ-producing type 1 T cells and produce a similar pattern of cytokines. Thus, the cells and mediators responsible for the PMN recruitment into skin, joints, or gut during DTHRs remain unknown. Analyzing hapten-induced DTHRs of the skin, we found that mast cells determine the T cell-dependent PMN recruitment through two mediators, tumor necrosis factor (TNF) and the CXC chemokine macrophage inflammatory protein 2 (MIP-2), the functional analogue of human interleukin 8. Extractable MIP-2 protein was abundant during DTHRs in and around mast cells of wild-type (WT) mice but absent in mast cell-deficient WBB6F1-Kit(W)/Kit(W-v) (Kit(W)/Kit(W-v)) mice. T cell-dependent PMN recruitment was reduced >60% by anti-MIP-2 antibodies and >80% in mast cell-deficient Kit(W)/Kit(W-v) mice. Mast cells from WT mice efficiently restored DTHRs and MIP-2-dependent PMN recruitment in Kit(W)/Kit(W-v) mice, whereas mast cells from TNF(-/-) mice did not. Thus, mast cell-derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell-mediated DTHRs.

Original languageEnglish
Pages (from-to)1441-1451
Number of pages11
JournalJournal of Experimental Medicine
Volume192
Issue number10
DOIs
StatePublished - 20 Nov 2000
Externally publishedYes

Keywords

  • Autoimmune disease
  • Chemokines
  • Cytokines
  • Inflammation
  • Type 1 T cells

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