Abstract
We have recently shown that the leukotriene B(4) (LTB(4))-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 IFNgamma 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 LTB(4)-BLT1 lipid chemoattractant pathway in human T-cell responses, and how it may link innate and adaptive immunity.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP-ribosyl Cyclase 1* / immunology
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ADP-ribosyl Cyclase 1* / metabolism
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Acute Disease
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Asthma / immunology*
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Bronchoalveolar Lavage Fluid / cytology
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Case-Control Studies
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Cells, Cultured
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Epstein-Barr Virus Infections / immunology*
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Epstein-Barr Virus Infections / metabolism
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HLA-DR Antigens* / immunology
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HLA-DR Antigens* / metabolism
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Herpesvirus 4, Human / isolation & purification
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Humans
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Inflammation
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Interferon-gamma / metabolism
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Interleukin-4 / metabolism
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Leukotriene B4 / metabolism
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Lymphocyte Activation
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Protein Serine-Threonine Kinases / metabolism
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Receptors, CCR2
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Receptors, CCR6
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Receptors, Chemokine / metabolism
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Receptors, Interleukin-8A / metabolism
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Receptors, Leukotriene B4 / genetics
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Receptors, Leukotriene B4 / immunology*
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Receptors, Leukotriene B4 / metabolism
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Receptors, Purinergic P2 / genetics
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Receptors, Purinergic P2 / immunology*
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Receptors, Purinergic P2 / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
Substances
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CCR2 protein, human
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CCR6 protein, human
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Ccr2 protein, mouse
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HLA-DR Antigens
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LTB4R protein, human
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Receptors, CCR2
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Receptors, CCR6
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Receptors, Chemokine
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Receptors, Interleukin-8A
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Receptors, Leukotriene B4
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Receptors, Purinergic P2
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Leukotriene B4
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Interleukin-4
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Interferon-gamma
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SNF1-related protein kinases
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Protein Serine-Threonine Kinases
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ADP-ribosyl Cyclase 1