T Cell Differentiation within an Innovative Three-Dimensional Collagen Matrix
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The vertebrate immune system is comprised of two branches: humoral immunity and cell-mediated immunity. A key coordinator of these immune responses is the T helper cell. Upon activation a T helper cell can differentiate into two subsets: T helper type 1and T helper type 2 (Th l and Th 2 respectively) according to the cytokines that they produce. Although much is known about the signaling pathways leading to Th l cellular differentiation, little is known about the pathways leading to the development of the Th 2 subset. Studies conducted in liquid culture have indicated that T cell differentiation is mediated through the formation of a stable aggregate between the naive T cell and the antigen presenting cell (APC). Liquid culture studies have shown a predominate shift towards Th l differentiation over Th 2 differentiation in T helper cell/APC aggregates. However, recent studies that utilized a three dimensional collagen matrix in order to (T cell locomotion in an in situ environment found that T cells do not form long lasting aggregates with APCs. In this study a novel collagen matrix assay was used to study T helper cell differentiation under modified culture conditions which simulated in situ conditions. Results indicated that the collagen conditions increased Th 2 cytokine production which indicated a shift towards Th 2 differentiation opposed to the predominant Th l differentiation previously observed in liquid cultures. These results suggest that the previous paradigm describing Th l/Th 2 differentiation may not accurately describe in situ parameters.