Nature immunology
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Studies in both humans and rodents indicate that CD8+ T cells may be important in allergic inflammation. However, neither the mechanisms that mediate CD8+ T cell recruitment to inflamed tissues nor the relative participation of effector and central memory CD8+ T cells is known. Here we report that activated mast cells induced chemotaxis of effector, but not central memory, CD8+ T cells through production of leukotriene B4 (LTB4). These studies indicate that LTB4 production by activated peripheral leukocytes could be important for the recruitment of effector CD8+ T cells to sites of inflammation.
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Leukotriene B4 (LTB4) was originally described as a potent lipid myeloid cell chemoattractant, rapidly generated from innate immune cells, that activates leukocytes through the G protein-coupled receptor BLT1. We report here that BLT1 is expressed on effector CD4+ T cells generated in vitro as well as in vivo when effector T cells migrate out of the lymphoid compartment and are recruited into peripheral tissues. BLT1 mediated LTB4-induced T helper type 1 (T(H)1) and T(H)2 cell chemotaxis and firm adhesion to endothelial cells under flow, as well as early CD4+ and CD8+ T cell recruitment into the airway in an asthma model. Our findings show that the LTB4-BLT1 pathway is involved in linking early immune system activation and early effector T cell recruitment.
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Leukotriene B4 (LTB4) is a potent chemoattractant for myeloid leukocytes, which express BLT1, the high-affinity receptor for LTB4. We report here that BLT1 is induced substantially in CD8+ effector T cells and at lower amounts in CD8+ central memory T cells. ⋯ In competitive homing experiments, wild-type effector cells were three times more efficient at migrating to the inflamed peritoneal cavity than were BLT-deficient effector cells. These results identify LTB4-BLT1 as a potent nonchemokine pathway for cytotoxic effector cell traffic.