ReviewStop and Go Traffic to Tune T Cell

1971). The details of the in vivo search process have been examined only recently, but some insights into New York University School of Medicine 540 First Avenue antigen-specific T cell-APC interactions have been generated by in vitro studies. New York, New York 10021 In vitro antigen-specific T cell-APC interactions were observed as early as the 1970s when in vitro antigen-specific T cell systems were first emerging and in early studies of T cells interacting with dendritic cells (Inaba Adaptive immune responses are initiated by interactions of T cells with antigen-presenting cells, but the and Steinman, 1986; Lipsky and Rosenthal, 1975). The duration of these interactions varies with the function. basic nature of these interactions during an immune response in vivo has been a matter of speculation. While Effector cells can execute functions rapidly and may only require a few minutes, whereas naive T cells require some in vitro systems provide evidence for stable interactions , referred to as immunological synapses, several hours of interaction with antigen-presenting cells to induce proliferation and cytokine production compelling evidence supports T cell activation through serial transient interactions. Deep tissue intravital and (Iezzi et al., 1998; van Stipdonk et al., 2003). It has been demonstrated that sustained TCR signaling is needed organ culture microscopy studies suggest that both modes of interaction are employed, but new issues to induce rearrangement of chromatin required for cyto-kine gene expression, at least in the case of induction have emerged. This review will discuss in vitro results that framed the hypotheses that are currently being of Th2 effector T cells from naive T cells (Iezzi et al., 1999). These studies were performed under conditions tested in vivo. I present a model in which TCR stop signals compete with chemokine-mediated go signals where the T cells were in continuous contact with anti-gen but did not examine the nature of this interaction, to adjust the duration of immunological synapse formation and tune the immune response between toler-whether the T cells stayed in place or migrated rapidly over the surface, or if they interacted in phases that ance and full activation. mixed these modes of interaction over the critical time period. In this review I will summarize the in vitro results that framed the question for recent in vivo observations, Introduction The interaction of T cells with antigen-presenting cells discuss the initial results from in vivo imaging of T cell-APC interactions, and then …