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Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues

Nature Immunology volume 4, pages 965–973 (2003)Cite this article

Abstract

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. LTB4 elicited BLT1-dependent chemotaxis in effector cells, but not in naive or central memory cells. Intravital microscopy showed that BLT1 signaling induced rapid integrin-mediated arrest of rolling effector and central memory cells in postcapillary venules. 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.

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Figure 1: Strong induction of BLT1 in activated CD8+ T cells after exposure to IL-2, but not IL-15.
Figure 2: LTB4 concentration gradients induce selective BLT1-dependent chemotaxis of TEFF cells.
Figure 3: Inhibition of LTB4-mediated chemotaxis of wild-type TEFF cells by CP-105,696.
Figure 4: LTB4 superfusion of inflamed mouse cremaster muscle induces rapid BLT1-dependent accumulation of TEFF and TCM cells in postcapillary venules.
Figure 5: Rolling and sticking of wild-type and BLT1-deficient TEFF and TCM cells in cremaster muscle venules before and during LTB4 superfusion.
Figure 6: BLT1 is required for efficient TEFF cell recruitment to the inflamed peritoneal cavity.

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Acknowledgements

We thank C. Schweitzer, B. Reinhardt and G. Cheng for technical support, and J. Moore for editorial assistance. We also thank W. Weninger and I. Mazo for advice and discussions. This work was supported by a National Institutes of Health T32 Transfusion Biology and Medicine Training Grant from Children's Hospital, Boston (to K.G. and M.G.) and by National Institutes of Health grants HL48675, HL54936 and HL56949 to U.H.v.A; HL04087 to A.M.T.; and AI050892, AI46999 and DK5005 to A.D.L.

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Authors and Affiliations

  1. Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Katayoon Goodarzi, Mahmoud Goodarzi & Ulrich H von Andrian

  2. Division of Rheumatology, Center for Immunology and Inflammatory Diseases, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Andrew M Tager & Andrew D Luster

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Correspondence to Ulrich H von Andrian.

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Goodarzi, K., Goodarzi, M., Tager, A. et al. Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Nat Immunol 4, 965–973 (2003). https://doi.org/10.1038/ni972

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