Specialized microenvironment within the lymph node controls antigen-presentation properties of dendritic cells and Th2 differentiation. (P1119)

Abstract

Abstract T cells need to encounter antigen-bearing dendritic cells (DCs) to undergo clonal expansion and effector development. These interactions, within lymphoid tissues, are orchestrated by the expression of chemokines and chemokine receptors. Indeed, CCR7 expression by both T cells and DCs is thought to facilitate DC/T cell encounters within the T cell area of the lymph node. However, it is unknown whether co-localization of the DCs and T cells within the T cell area is obligate for effector generation. Here, we show that, following infection with an intestinal nematode, antigen-bearing DCs and the responding CD4+ T cells upregulate expression of CXCR5 and migrate in a CXCR5/CXCL-13 dependent fashion to the B cell area of the mesenteric lymph node. We further demonstrate that CXCR5-dependent localization of DCs and T cells near the CXCL13-expressing B cell follicles are required for optimal Th2 responses. Furthermore, we found that disrupting DCs from accumulating in the perifollicular region prevents the DCs from initiating Th2 differentiation. Finally, we demonstrated that DCs receive conditioning signals within the perifollicular microenvironment that change Class II Transactivator (CIITA) expression, maturation and antigen-presenting properties of DCs that allow the DCs to initiate Th2 priming. These results show that specialized microenvironments within the lymph node directly influence dendritic cell antigen presentation and function for effective priming of Th2 responses.