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Mast Cells Control Neutrophil Recruitment during T Cell–Mediated Delayed-Type Hypersensitivity Reactions through Tumor Necrosis Factor and Macrophage Inflammatory Protein 2

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...

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Detalles Bibliográficos
Autores principales: Biedermann, Tilo, Kneilling, Manfred, Mailhammer, Reinhard, Maier, Konrad, Sander, Christian A., Kollias, George, Kunkel, Steven L., Hültner, Lothar, Röcken, Martin
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193186/
https://www.ncbi.nlm.nih.gov/pubmed/11085746
Descripción
Sumario: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 WBB6F(1)-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.