title: CXCR3 is required for migration to dermal inflammation by normal and in vivo activated T cells: differential requirements by CD4 and CD8 memory subsets.
abstract: Lymphocytes in inflamed tissues express numerous chemokine receptors. The relative importance of these receptors for migration in inflammation is unclear. The role of CXCR3 in T cell subset migration was examined using monoclonal antibodies developed to rat CXCR3. CXCR3 was expressed on sixfold more CD8(+) ( approximately 30%) than CD4(+) ( approximately 5%) T cells in spleen, lymph nodes and blood, and on approximately 10% of CD4(+)CD45RC(-) (memory) and approximately 50% of CD8(+)CD45RC(+) spleen T cells. After immunization, CXCR3 increased tenfold on CD4(+) lymph node lymphoblasts ( approximately 55%), and >90% of inflammatory exudate T cells were CXCR3(+). CXCR3(+) T cells migrated significantly better than CXCR3(-) T cells to all dermal inflammatory stimuli tested in vivo, even though these T cells are a minority of the memory T cells. Blocking CXCR3 inhibited recruitment of 60-85% of unstimulated T cells and up to 90% of CD8(+)CD45RC(+) effector T cells, but caused <50% inhibition of CD4(+) and CD8(+) memory (CD45RC(-)) T cells. About 90% of T lymphoblast migration to IFN-gamma, IFN-gamma plus TNF-alpha, polyinosinic polycytidylic acid, lipopolysaccharide, and delayed-type hypersensitivity (DTH)-induced inflammation was inhibited. Blockade also reduced DTH-induced induration. Thus, CXCR3 has a non-redundant role in T cell migration to dermal inflammation and is critical for activated T lymphoblast recruitment, but memory T cells are less dependent on CXCR3 for their infiltration.
authors.affiliation: Department of Pediatrics, Dalhousie University, Halifax, Canada.
authors.forename: Karkada
authors.initials: K
authors.lastname: Mohan
authors.forename: Erin
authors.initials: E
authors.lastname: Cordeiro
authors.forename: Maria
authors.initials: M
authors.lastname: Vaci
authors.forename: Christopher
authors.initials: C
authors.lastname: McMaster
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Issekutz
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D002448:Cell Adhesion; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D006224:Cricetinae; D003872:Dermatitis / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis / Q000502:physiology*; D013154:Spleen / Q000276:immunology
chemical_list: C515188:Cxcr3 protein, mouse; C515189:Cxcr3 protein, rat; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine