Trends in Immunology
OpinionCXCR5+ T cells: follicular homing takes center stage in T-helper-cell responses
Section snippets
CXCR5 identifies follicular-homing T helper cells
CXCR5 is expressed on a subset of peripheral-blood and tonsillar memory CD4+ T cells, but is absent from naive CD4+ T cells, and T helper 1 (Th1) and Th2 cells (Table 1) 12., 13., 14., 15.. In addition, CXCR5 is present on a minor subset (<2%) of blood memory CD8+ T cells. In the tonsils, CXCR5+ T cells are highly enriched (>95% of CD4+CD45RO+ T cells) and express activation markers, but lack the capacity to participate in inflammatory responses, as indicated by the absence of receptors for
Rapid induction of CXCR5 during Th-cell activation
CXCR5 is expressed rapidly on T cells during primary immune responses in mice, and the follicular localization of these T cells was shown to depend on adjuvant 25., 26.. This is in agreement with previous reports describing the one-way traffic of newly activated CD4+ T cells into B-cell follicles 27., 28., 29., 30., 31.. Notably, OX40 (CD134) signaling was shown to be linked with the expression of CXCR5 by T cells and T-cell relocation into follicles [32]. The in vitro induction of CXCR5
TFH cells at the gateway of effector Th-cell generation
The early acquisition of expression of CXCR5 during Th-cell activation indicates that the follicular-homing capability of TFH cells is linked intimately with the priming process, which precedes cellular differentiation into bona fide effector cells. It follows that all types of effector Th cell, including Th1 and Th2 cells, which are programmed to enter inflammatory sites in the periphery (Table 1), as well as B-helper T cells, which control germinal-center reactions in the B-cell zone, are
Concluding remarks
This discussion is based primarily on our knowledge of chemokine-mediated lymphocyte traffic. For that reason, we propose an enforced, rather than diffusion-driven, relocation of TFH cells, which are Ag-primed but not yet polarized, from the site of initial Ag contact in the T-cell zone to the B-cell compartment. Our speculation about the further development of TFH cells within follicles involves ICOSL+ B cells (ICOSL expression on CXCR5+ DCs has yet to be shown) as alternative APCs for
Acknowledgements
This work was supported by grant 31-055996.98 from the Swiss National Science Foundation and grant 99.0471-5 from the Bundesamt für Bildung und Wissenschaft.
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