| First Author | Moore TV | Year | 2011 |
| Journal | Am J Respir Cell Mol Biol | Volume | 45 |
| Issue | 4 | Pages | 843-50 |
| PubMed ID | 21421907 | Mgi Jnum | J:190213 |
| Mgi Id | MGI:5448381 | Doi | 10.1165/rcmb.2010-0466OC |
| Citation | Moore TV, et al. (2011) Inducible costimulator controls migration of T cells to the lungs via down-regulation of CCR7 and CD62L. Am J Respir Cell Mol Biol 45(4):843-50 |
| abstractText | 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. |
