Oral Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

Cellular dynamics of adaptive immune responses in the lymph node (#10)

Takaharu Okada 1
  1. RIKEN Center of Intergrative Medical Science Center, Kanagawa, Japan

The immune tissues such as lymph nodes are dynamically compartmentalized so that relevant cell types for each mode of immune responses are co-localized and able to access each other. In this talk, I will discuss (1) mechanisms of helper T cell localization in germinal centers and (2) dynamics of cross-presenting dendritic cells in skin-draining lymph nodes. (1) Follicular helper T (Tfh) cells access the B cell follicle to promote antibody responses, and are particularly important for germinal center (GC) reactions. However, the molecular mechanisms of how Tfh cells are physically associated with GCs are incompletely understood. We have found that the sphingosine-1-phosphate receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were ineffective in supporting GC and recall antibody responses compared to T cells deficient only in CXCR5. These results suggest that S1PR2-driven Tfh cell retention in GCs contributes to GC and memory antibody responses.(2) Cytotoxic T cells are known to be generated through interactions of antigen-specific CD8+ T cells with DCs that cross-present antigen. In skin-draining lymph nodes, there are two subsets of cross-presenting DCs, namely CD103+ migratory DCs immigrating from the skin and CD8+ lymph node-resident DCs. However, spatio-temporal regulation of their interactions with CD8+ T cells is poorly understood. We have developed methods that allow visualization of these two subsets of cross-presenting DCs in the lymph node. Two-photon microscopy analysis suggested differential contribution of the cross-presenting DC subsets to activation of antigen-specific CD8+ T cells. Furthermore, our results started to reveal previously unknown compartmentalization of the DC subsets within the T cell zone of the lymph node.