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

T Biedermann, M Kneilling, R Mailhammer… - The Journal of …, 2000 - rupress.org
T Biedermann, M Kneilling, R Mailhammer, K Maier, CA Sander, G Kollias, SL Kunkel…
The Journal of experimental medicine, 2000rupress.org
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 …
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-KitW/KitW-v (KitW/KitW-v) mice. T cell–dependent PMN recruitment was reduced >60% by anti–MIP-2 antibodies and >80% in mast cell–deficient KitW/KitW-v mice. Mast cells from WT mice efficiently restored DTHRs and MIP-2–dependent PMN recruitment in KitW/KitW-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.
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