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

Abstract

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 IFNγ 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.