T cell Differentiation within an Innovative Three-Dimensional Collagen Matrix
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 1 and T helper type 2 (Th1 and Th2 respectively) according to the cytokines that they produce. Although much is known about the signaling pathways leading to Th1 cellular differentiation, little is known about the pathways leading to the development of the Th2 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 Th1 differentiation over Th2 differentiation in T helper cell/APC aggregates. However, recent studies that utilized a three dimensional collagen matrix in order to IT cell locomotion in an in situ environment found that T cells do not form long lasting aggregates with APCs. In the present 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 Th2 cytokine production which indicated a shift towards Th2 differentiation opposed to the predominant Th1 differentiation previously observed in liquid cultures. These results suggest that the previous paradigm describing Th1/ITh2 differentiation may not accurately describe in situ parameters.
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