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 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 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.
Biedermann
T
T
Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, 80337 Munich, Germany.
Kneilling
M
M
Mailhammer
R
R
Maier
K
K
Sander
C A
CA
Kollias
G
G
Kunkel
S L
SL
Hültner
L
L
Röcken
M
M
D000818:Animals; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015846:Monokines / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D010853:Picryl Chloride; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D019009:Proto-Oncogene Proteins c-kit; D010853:Picryl Chloride