title: Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation.
abstract: Th cell access to primary B cell follicles is dependent on CXCR5. However, whether CXCR5 induction on T cells is sufficient in determining their follicular positioning has been unclear. In this study, we find that transgenic CXCR5 overexpression is not sufficient to promote follicular entry of naive T cells unless the counterbalancing influence of CCR7 ligands is removed. In contrast, the positioning of Ag-engaged T cells at the B/T boundary could occur in the absence of CXCR5. The germinal center (GC) response was 2-fold reduced when T cells lacked CXCR5, although these T cells were able to access the GC. Finally, CXCR5(high)CCR7(low) T cells were found to have elevated IL-4 transcript and programmed cell death gene-1 (PD-1) expression, and PD-1(high) cells were reduced in the absence of T cell CXCR5 or in mice compromised in GC formation. Overall, these findings provide further understanding of how the changes in CXCR5 and CCR7 expression regulate Th cell positioning during Ab responses, and they suggest that development and/or maintenance of a PD-1(high) follicular Th cell subset is dependent on appropriate interaction with GC B cells.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Haynes
authors.forename: Christopher D C
authors.initials: CD
authors.lastname: Allen
authors.forename: Robin
authors.initials: R
authors.lastname: Lesley
authors.forename: K Mark
authors.initials: KM
authors.lastname: Ansel
authors.forename: Nigel
authors.initials: N
authors.lastname: Killeen
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D061026:Programmed Cell Death 1 Receptor; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000502:physiology*; D054380:Receptors, CXCR5 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C513179:CXCR5 protein, mouse; C515371:Ccr7 protein, mouse; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D054400:Receptors, CCR7; D054380:Receptors, CXCR5