that in addition to CXCR5 expression, T cells require a second signal to be directed to follicles. As up to 10% of GC cells represent antigen-specific CD4 cells (24), one is tempted to speculate that this signal is provided at the time of T–B cell interaction, as this would privilege antigen-spe- cific cells to migrate to the follicles. Once within the folli- cles, a large proportion of the activated T cells has lost CCR7 but expresses ICOS (17) and has intracellular stores of CD154 (Fig. 2 C). ICOS has been shown to induce pro- duction of various cytokines from recently activated T cells and to critically participate in T cell–dependent immune responses (17, 25). Furthermore, the interaction of CD154 with its receptor, CD40, is an essential step during a T cell– dependent B cell response. Data derived from CD40- and CD154-deficient mice demonstrate that this interaction regulates proliferation of B cells, Ig class switching, and Ab production (16). The data presented here show that CXCR51 CD4 cells homing to B cell follicles express ICOS, CD154, and IL-10. Consequently, when cocultur- ing sorted tonsillar T cells with B cells, we observed Ig pro- duction only within the CXCR51 fraction, thus identify- ing this cell population as the classical Th cells. Our observation of long-lived memory cells not being present within the pool of peripheral recirculating CXCR51 CD4 cells is in accordance with the idea that CXCR51 CD4 cells represent recently activated effector cells. Given the fact that GCs usually disappear within ,4 wk, together with the observation that virtually all CXCR51 tonsillar CD4 cells coexpress CD95, which renders them highly sus- ceptible towards apoptosis, it seems likely that CXCR51 CD4 cells do not contribute to the long-lived memory pool. However, we cannot currently exclude that some CXCR51 CD4 cells lose CXCR5 expression, thus revert- ing to a phenotype (i.e., CXCR52CD45RO1) associated with T cell memory. Independent of their origin, a consid- erable part of the long-lived central memory CD4 cells has to maintain or regain sufficient levels of CCR7 to continu- ously recirculate through secondary lymphoid organs in or- der to initiate a second wave of antigen-specific T cells once rechallenged with previously encountered antigens. In summary, this study adds weight to the notion that the pattern of expressed chemokine receptors functionally characterizes T cell populations (26). It was demonstrated that CXCR5 is expressed on T cells situated in GCs and follicles, which express costimulatory molecules (CD40L, ICOS) required for B cell maturation and survival. Based on the cytokines expressed, CXCR51 T cells do not fall into the Th1/Th2 classification but represent an effector subset that is involved in B cell help. As these cells show all characteristics required for effi- cient B cell help within lymphoid follicles, we suggest call- ing these cells “follicular B helper T cells” (TFH). 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