Imaging of T-cell interactions with antigen presenting cells in culture and in intact lymphoid tissue.

Abstract

The development of an effective immune response requires cell-cell contact between T cells and antigen-bearing cells of several types (dendritic cells, B cells, infected tissue cells). Recent advances in light microscopy have led to intense investigation of the molecular events that accompany these cell interactions, especially the redistribution of membrane proteins into discrete organized subdomains within the zone of cell-cell contact termed the 'immunological synapse'. Here we discuss two aspects of our own studies in this area. First, we highlight results from our in vitro analysis of the role of the cytoskeletal ezrin, radixin, moesin adapter proteins in the exclusion of CD43 from the well-defined T cell receptor (TCR) and integrin-rich zones of the synapse. Based on the molecular mechanism uncovered in this work, we propose a new model for how TCR-signaled changes in cytoskeletal organization indirectly influence both protein distributions and the efficiency of signaling between T cell and presenting cell. We then discuss the development of a new method for dynamic visualization of T cell - dendritic cell interactions in intact lymphoid tissue. The remarkable longevity of monogamous lymphocyte-presenting cell interactions is discussed, differences between our observations and those of others are laid out in detail, and prospects for future application of this technical approach to analysis of early immune responses in lymphoid organs and of effector lymphocyte function in tissues are presented.