The leukotriene B4 lipid chemoattractant receptor BLT1 defines antigen-primed T cells in humans.
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.
Islam
Sabina A
SA
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Thomas
Seddon Y
SY
Hess
Christoph
C
Medoff
Benjamin D
BD
Means
Terry K
TK
Brander
Christian
C
Lilly
Craig M
CM
Tager
Andrew M
AM
Luster
Andrew D
AD
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology / Q000378:metabolism; D000208:Acute Disease; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016022:Case-Control Studies; D002478:Cells, Cultured; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008213:Lymphocyte Activation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054390:Receptors, CCR2; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
C515334:CCR2 protein, human; C106311:CCR6 protein, human; C515335:Ccr2 protein, mouse; D006684:HLA-DR Antigens; C513240:LTB4R protein, human; D054390:Receptors, CCR2; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D023062:Receptors, Interleukin-8A; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D007975:Leukotriene B4; D015847:Interleukin-4; D007371:Interferon-gamma; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D051997:ADP-ribosyl Cyclase 1