Defining the roles of calcium mobilization in the initial decondensation of chromatin during T cell activation (P1162)

Abstract

Condensation of chromatin within the nucleus of T lymphocytes occurs during thymocyte development and is a requirement for proper T cell development and maintenance of the naïve (quiescent) state. T cell activation via stimulation of the T cell receptor (TCR) is a necessary step in an immune response, allowing T cells to gain the ability to proliferate in response to cytokines, such as IL-2. During this activation process, the chromatin within T cells decondenses, allowing access to the previously inaccessible DNA, permitting the transcription of genes required for proliferation. We demonstrate that stimulation of either the IP¬3 (inositol triphosphate) or DAG (diacylglycerol) pathways downstream of the TCR leads to chromatin decondensation, but with different kinetics. Within the IP3 pathway, we show that extracellular calcium is not required for the initial decondensation of chromatin. Furthermore, we show that the release of calcium from intracellular stores is sufficient and required for the initial decondensation of chromatin following TCR engagement. Interestingly, while calcium mobilization results in a decondensation of chromatin, it is not sufficient for STAT5 target gene expression. However, chromatin decondensation via the DAG pathway is capable of making T cells competent to respond to IL-2. These findings suggest that there may be at least two distinct domains of condensed chromatin in naïve T cells.