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Blood, 15 January 2006, Vol. 107, No. 2, pp. 444-453.
Prepublished online as a Blood First Edition Paper on September 22, 2005; DOI 10.1182/blood-2005-06-2362.


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CHEMOKINES, CYTOKINES, AND INTERLEUKINS

The leukotriene B4 lipid chemoattractant receptor BLT1 defines antigen-primed T cells in humans

Sabina A. Islam, Seddon Y. Thomas, Christoph Hess, Benjamin D. Medoff, Terry K. Means, Christian Brander, Craig M. Lilly, Andrew M. Tager, and Andrew D. Luster

From the Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, and the Division of Infectious Diseases, and the Partners AIDS Research Center, Massachusetts General Hospital, and the Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

We have recently shown that the leukotriene B4 (LTB4)–BLT1 pathway is important in early effector T-cell recruitment in mouse models of inflammation. Here we characterize the phenotype and function of human peripheral blood BLT1+ T cells in health and illustrate their involvement in asthma and acute infection. In healthy individuals, BLT1+ T cells are a rare peripheral blood T-cell population enriched for the activation markers CD38 and HLA-DR. Compared with BLT1 T cells, a larger proportion of peripheral blood BLT1+ T cells express the effector cytokines IFN{gamma} and IL-4 and inflammatory chemokine receptors, CCR1, CCR2, CCR6, and CXCR1. Consequently, in healthy individuals peripheral blood BLT1+ T cells are a rare antigen-primed T-cell subset with unique phenotypic, migratory, and functional properties. BLT1 expression on T cells is tightly regulated by inflammation and only transiently expressed after naive T-cell activation by dendritic cells. Although rare in the peripheral blood of healthy individuals, BLT1+ T cells are markedly increased in frequency in the peripheral blood in response to acute Epstein-Barr virus (EBV) infection and moderately increased in the airways of asymptomatic allergic asthmatics. Our studies provide novel insights into the LTB4-BLT1 lipid chemoattractant pathway in human T-cell responses, and how it may link innate and adaptive immunity.


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