Mechanisms and Dynamics of T Cell-Mediated Cytotoxicity In Vivo

Abstract

Cytotoxic T lymphocytes (CTLs) are critical in the elimination of infected or malignant cells and are emerging as a major therapeutic target. How CTLs recognize and kill harmful cells has been characterized in vitro but little is known about these processes in the living organism. Here we review recent insights into CTL-mediated killing with an emphasis on in vivo CTL biology. Specifically, we focus on the possible rate-limiting steps determining the efficiency of CTL-mediated killing. We also highlight the need for cell-based datasets that permit the quantification of CTL dynamics, including CTL location, migration, and killing rates. A better understanding of these factors is required to predict protective CD8 T cell immunity in vivo and to design optimized vaccination protocols.

Keywords: cell migration; cellular immunity; chemokines; cytotoxic T cells; immunological synapses; immunotherapy; two-photon imaging.