Identification and Characterization of Specialized Antigen Presenting Cells in Rainbow Trout
As the oldest vertebrates to possess intact innate and adaptive immune systems fish are the ideal models to study evolution of adaptive immunity. With the advent of adaptive immunity came a new challenge: the coordination of temporally and spatially diverse responses to pathogens. In mammals, dendritic cells (DCs), as a result of their distinctive activation program and specialization in antigen presentation, function as a link between innate and adaptive immunity. The question as to whether dendritic cells arose concurrently with adaptive immunity or at a later date is unknown. It is possible that antigen presentation in fish is primarily accomplished by another cell type or types. The goal of my research was to identify the functional equivalent of mammalian dendritic cells in fish. In order to do this, significant numbers of cells were needed to enable functional characterization of presumptive dendritic cells. Dendritic cells are a rare cell type and in order to generate adequate numbers of cells for in depth analysis, protocols have been developed in mammals to culture dendritic cells. My approach to the problem, therefore, was to adapt these mammalian protocols to rainbow trout. Development of a hematopoietic culture system in rainbow trout, based on bone marrow derived DC cultures in mammals, generated DC-like cells (DCLCs) that were then characterized using criteria for classification of mammalian DCs. DCLCs resembled mammalian DCs in their expression of CD83 and MHCII, phagocytic capacity, and response to TLR-ligands; however, the most remarkable similarity was their ability to stimulate potent primary MLRs, more vigorous than those obtained with either macrophages or B-cells as stimulators. This evidence for a specialized antigen presenting cell type in rainbow trout has implications for fish vaccine development as well as comparative studies with mammals to elucidate the origins of adaptive immunity.