Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophageinflammatory protein 2

Polymorphonuclear leukocytes (PMNs) characterize the pathology of T cell-me diated autoimmune diseases and delayed-type hypersensitivity reactions (DTH Rs) in the skin, joints, and gut, but are absent in T cell-mediated autoimm une 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 recrui tment into skin, joints, or gut during DTHRs remain unknown. Analyzing hapt en-induced DTHRs of the skin, we found that mast cells determine the T cell -dependent PMN recruitment through two mediators, tumor necrosis factor (TN F) and the CXC chemokine macrophage inflammatory protein 2 (MIP-2), the fun ctional analogue of human interleukin 8. Extractable MIP-2 protein was abun dant during DTHRs in and around mast cells of wild-type (WT) mice but absen t 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 a nd >80% in mast cell-deficient Kit(W)/Kit(W-v) mice. Mast cells from WT mic e 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 cel ls during T cell-mediated DTHRs.