CXCR3 is required for migration to dermal inflammation by normal and in vivo activated T cells: differential requirements by CD4 and CD8 memory subsets.
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.
Mohan
Karkada
K
Department of Pediatrics, Dalhousie University, Halifax, Canada.
Cordeiro
Erin
E
Vaci
Maria
M
McMaster
Christopher
C
Issekutz
Thomas B
TB
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
C515188:Cxcr3 protein, mouse; C515189:Cxcr3 protein, rat; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine