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

Blood. 2006 Jan 15;107(2):444-53. doi: 10.1182/blood-2005-06-2362. Epub 2005 Sep 22.

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

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1* / immunology
  • ADP-ribosyl Cyclase 1* / metabolism
  • Acute Disease
  • Asthma / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Case-Control Studies
  • Cells, Cultured
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / metabolism
  • HLA-DR Antigens* / immunology
  • HLA-DR Antigens* / metabolism
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Inflammation
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Leukotriene B4 / metabolism
  • Lymphocyte Activation
  • Protein Serine-Threonine Kinases / metabolism
  • Receptors, CCR2
  • Receptors, CCR6
  • Receptors, Chemokine / metabolism
  • Receptors, Interleukin-8A / metabolism
  • Receptors, Leukotriene B4 / genetics
  • Receptors, Leukotriene B4 / immunology*
  • Receptors, Leukotriene B4 / metabolism
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / immunology*
  • Receptors, Purinergic P2 / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • CCR2 protein, human
  • CCR6 protein, human
  • Ccr2 protein, mouse
  • HLA-DR Antigens
  • LTB4R protein, human
  • Receptors, CCR2
  • Receptors, CCR6
  • Receptors, Chemokine
  • Receptors, Interleukin-8A
  • Receptors, Leukotriene B4
  • Receptors, Purinergic P2
  • Leukotriene B4
  • Interleukin-4
  • Interferon-gamma
  • SNF1-related protein kinases
  • Protein Serine-Threonine Kinases
  • ADP-ribosyl Cyclase 1