Identification of antigen-presenting cells for memory T helper cells in the recall response

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Immunological memory provides long-term protective immunity against pathogens that have been encountered before. Memory is maintained by memory cells, generated in the primary challenge. Recall response is an intimate collaboration between long-lived memory B and memory T helper (Th) cells, resulting in long-lasting humoral protection, due to specific antibodies secreted by long-lived plasma cells. However, it remains unclear how the two memory cells induce the recall response. Only recently, I could show that memory Th cells are mostly maintained as resting cells in distinct survival niches of the bone marrow (BM) and that these cells are required for the differentiation of memory B cells into long-lived plasma cells in the recall response. This novel findings warrant a basic reinvestigation of how recall response is mounted. In the project proposed, I will track memory Th cells from the memory phase into the recall reaction by advanced cytometry and advanced microscopy, to (1) identify antigen-presenting cells (APCs) for memory Th cells in the BM by visualizing cell-cell interaction and inducing serological depletion and genetic dysfunction and (2) identify co-stimulatory signals involved in the reactivation of memory Th cells in the recall response.