title: Inducible costimulator controls migration of T cells to the lungs via down-regulation of CCR7 and CD62L.
abstract: We and others reported that inducible costimulator-deficient (ICOS(-/-)) mice manifest a defect in Th2-mediated airway inflammation, which was attributed to reduced Th2 differentiation in the absence of ICOS signaling. Interestingly, the number of CD4 T cells present in the airways and lungs after sensitization and challenge is significantly reduced in ICOS(-/-) mice. We now show that this reduction is not attributable simply to a reduced proliferation of ICOS(-/-) cells, because significantly more ICOS(-/-) than wild-type activated CD4 T cells are present in the lymph nodes, suggesting that more ICOS(-/-) CD4 T cells than wild-type CD4 T cells migrated into the lymph nodes. Further investigation revealed that activated ICOS(-/-) CD4 T cells express higher concentrations of the lymph node homing receptors, CCR7 and CD62L, than do wild-type CD4 T cells, leading to a preferential return of ICOS(-/-) cells to the nondraining lymph nodes rather than the lungs. Blocking reentry into the lymph nodes after the initiation of Th2-mediated airway inflammation equalized the levels of CD4 and granulocyte infiltration in the lungs of wild-type and ICOS(-/-) mice. Our results demonstrate that in wild-type CD4 T cells, co-stimulation with ICOS promotes the down-regulation of CCR7 and CD62L after activation, leading to a reduced return of activated CD4 T cells to the lymph nodes and a more efficient entry into the lungs.
authors.affiliation: Committee on Immunology and Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
authors.forename: Tamson V
authors.initials: TV
authors.lastname: Moore
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Clay
authors.forename: Judy L
authors.initials: JL
authors.lastname: Cannon
authors.forename: Alexander
authors.initials: A
authors.lastname: Histed
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Shilling
authors.forename: Anne I
authors.initials: AI
authors.lastname: Sperling
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D000947:Antigens, Helminth / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D015536:Down-Regulation; D060889:Inducible T-Cell Co-Stimulator Protein; D019041:L-Selectin / Q000378:metabolism*; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000235:genetics / Q000276:immunology*; D054400:Receptors, CCR7 / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000947:Antigens, Helminth; C515371:Ccr7 protein, mouse; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D054400:Receptors, CCR7; D019041:L-Selectin