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Original Article

^a Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, 80337 Munich, Germany
^b Institute of Clinical Molecular Biology and Tumor Genetics, 81377 Munich, Germany
^c Institute of Inhalation Biology, GSF–National Research Center for Environment and Health, 80807 Munich, Germany
^d Hellenic Pasteur Institute, 11521 Athens, Greece
^e Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, Frauenlobstr. 9-11, 80337 Munich, Germany.49-89-5160-620649-89-5160-6205

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 –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.

Key Words: chemokines • inflammation • type 1 T cells • cytokines • autoimmune disease

Abbreviations used in this paper: BMMC, bone marrow–derived mast cell; CHSR, contact hypersensitivity reaction; DTHR, delayed-type hypersensitivity reaction; EAE, experimental allergic encephalomyelitis; IP, IFN- inducible protein; KC, cytokine-induced neutrophil chemoattractant; MIP, macrophage inflammatory protein; MPO, myeloperoxidase; TNCB, trinitrochlorobenzene; WT, wild-type.

© 2000 The Rockefeller University Press

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