title: CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells.
abstract: CD1d-restricted T cells (NKT cells) are innate memory cells activated by lipid Ags and play important roles in the initiation and regulation of the immune response. However, little is known about the trafficking patterns of these cells or the tissue compartment in which they exert their regulatory activity. In this study, we determined the chemokine receptor profile expressed by CD1d-restricted T cells found in the peripheral blood of healthy volunteers as well as CD1d-restricted T cell clones. CD1d-restricted T cells were identified by Abs recognizing the invariant Valpha24 TCR rearrangement or by binding to CD1d-Fc fusion tetramers loaded with alpha-GalCer. CD1d-restricted T cells in the peripheral blood and CD1d-restricted T cell clones expressed high levels of CXCR3, CCR5, and CCR6; intermediate levels of CXCR4 and CXCR6; and low levels of CXCR1, CCR1, CCR2, and CX(3)CR1, a receptor pattern often associated with tissue-infiltrating effector Th1 cells and CD8+ T cells. Very few of these cells expressed the lymphoid-homing receptors CCR7 or CXCR5. CCR4 was expressed predominantly on CD4+, but not on double-negative CD1d-restricted T cells, which may indicate differential trafficking patterns for these two functionally distinct subsets. CD1d-restricted T cell clones responded to chemokine ligands for CXCR1/2, CXCR3, CXCR4, CXCR6, CCR4, and CCR5 in calcium flux and/or chemotaxis assays. These data indicate that CD1d-restricted T cells express a chemokine receptor profile most similar to Th1 inflammatory homing cells and suggest that these cells perform their function in peripheral tissue sites rather than in secondary lymphoid organs.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Seddon Y
authors.initials: SY
authors.lastname: Thomas
authors.forename: Runhua
authors.initials: R
authors.lastname: Hou
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Boyson
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
authors.forename: Christoph
authors.initials: C
authors.lastname: Hess
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Olson
authors.forename: Jack L
authors.initials: JL
authors.lastname: Strominger
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gumperz
authors.forename: S Brian
authors.initials: SB
authors.lastname: Wilson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D055610:Antigens, CD1d; D001666:Binding Sites, Antibody; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002999:Clone Cells; D003656:Decidua / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000097:blood; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; D002118:Calcium