The Journal of Experimental Medicine
ThymUS '08
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Published online 13 November 2000.
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© The Rockefeller University Press, 0022-1007/2000/11/1441/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 10, November 20, 2000 1441-1452


Original Article

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

Tilo Biedermanna, Manfred Kneillinga, Reinhard Mailhammerb, Konrad Maierc, Christian A. Sandera, George Kolliasd, Steven L. Kunkele, Lothar Hültnerb, and Martin Röckena
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

Correspondence to: Martin Röcken, Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, Frauenlobstr. 9-11, 80337 Munich, Germany. Tel:49-89-5160-6205 Fax:49-89-5160-6206

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 {gamma}–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.

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


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