Licensing of naïve T cells for rapid TNF production (138.14)

Abstract

Abstract TNF is a potent inflammatory cytokine with numerous immunological functions, including the ability to limit the magnitude of virus-specific T cell responses during infection. Naïve T cells in secondary lymphoid organs (SLOs) exhibit a unique ability to produce TNF rapidly after activation and prior to acquiring other effector functions. Peripheral T cells are a heterogeneous population of cells at various stages of post-thymic development. To determine how maturation influences the licensing of T cells to produce TNF, we compared cytokine profiles of single positive thymic T cells, recent thymic emigrants (RTEs) and matured-naïve T cells during TCR activation. Thymic T cells exhibited a poor ability to produce TNF when compared to splenic T cells, despite possessing a similar potential for activation. Moreover, thymic T cells had significantly reduced levels of TNF message and phosphorylated MAPK (Erk1/2) when compared to their splenic counterparts. Stimulation of thymic T cells in the presence of splenic B cells and APCs partially licensed the T cells to produce TNF but not to the same extent as peripheral T cells. RTEs had a significantly enhanced ability to produce TNF as compared to thymic T cells, but fully matured naïve T cells were the most efficient TNF producers. Together, these findings suggest that TNF expression by naïve T cells is regulated via a gradual licensing process that requires functional maturation in peripheral lymphoid organs.