Rules of chemokine receptor association with T cell polarization in vivo

Citation
Ch. Kim et al., Rules of chemokine receptor association with T cell polarization in vivo, J CLIN INV, 108(9), 2001, pp. 1331-1339
Citations number
54
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF CLINICAL INVESTIGATION
ISSN journal
0021-9738 → ACNP
Volume
108
Issue
9
Year of publication
2001
Pages
1331 - 1339
Database
ISI
SICI code
0021-9738(200111)108:9<1331:ROCRAW>2.0.ZU;2-Z
Abstract
Current concepts of chemokine receptor (CKR) association with Th1 and Th2 c ell polarization and effector function have largely ignored the diverse nat ure of effector and memory T cells in vivo. Here, we systematically investi gated the association of 11 CKRs, singly or in combination, with CD4 T cell polarization. We show that Th1, Th2, Th0, and nonpolarized T cells in bloo d and tissue can express any of the CKRs studied but that each CKR defines a characteristic pool of polarized and nonpolarized CD4 T cells. Certain co mbinations of CKRs define populations that are markedly enriched in major s ubsets of Th1 versus Th2 cells. For example, although Th0, Th1, and Th2 cel ls are each found among blood CD4 T cells coordinately expressing CXCR3 and CCR4, Th1 but not Th2 cells can be CXCR3(+)CCR4(-), and Th2 but only rare Th1 cells are CCR4(+)CXCR3(-). Contrary to recent reports, although CCR7(-) cells contain a higher frequency of polarized CD4 T cells, most Th1 and Th 2 effector cells are CCR7(+) and thus may be capable of lymphoid organ homi ng. Interestingly, Th1-associated CKRs show little or no preference for Th1 cells except when they are coexpressed with CXCR3. We conclude that the co mbinatorial expression of CKRs, which allow tissue- and subset-dependent ta rgeting of effector cells during chemotactic navigation, defines physiologi cally significant subsets of polarized and nonpolarized T cells.