T cells as pioneers: antigen-specific T cells condition inflamed sites for high-rate antigen-non-specific effector cell recruitment.

Cellular infiltration is a classic hallmark of inflammation. Whereas the role of T cells in many types of inflammation is well established, the specific impact of antigen recognition on their migration into the site and on the accumulation of other effector cells are still matters of debate. Using a model of an inflammatory effector phase driven by T-cell receptor (TCR) transgenic T cells, we found (i) that antigen-specific T cells play a crucial role as 'pioneer cells' that condition the tissue for enhanced recruitment of further T effector cells and other leucocytes, and (ii) that the infiltration of T cells is not dependent on antigen specificity. We demonstrate that a small number of antigen-specific T cells suffice to initiate a cascade of cellular immigration into the antigen-loaded site. Although antigen drives this process, accumulation of T cells in the first few days of inflammation was not dependent on T-cell reactivity to the antigen. Both transgenic and wild-type T effector cells showed enhanced immigration into the site of antigen challenge after the initial arrival and activation of antigen-specific pioneer cells. This suggests that bystander accumulation of non-specific effector/memory T cells is a general feature in inflammation. Furthermore, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma were identified as mediators that contribute to conditioning of the inflammatory site for high-rate accumulation of T effector cells in this T-cell-driven model.