T cell activation and the cytoskeleton: you can't have one without the other

Abstract

More than a quarter of a century has passed since the observation that T cells rapidly polarize their actin and microtubule cytoskeletal systems toward antigen-presenting cells during activation. Since this initial discovery, several receptors on T cells (e.g., T cell receptor [TCR], co-receptors, integrins, and chemokine receptors) have been identified to regulate these two cytoskeletal networks through complex signaling pathways, which are still being elucidated. There is now an undeniable body of biochemical, pharmacological, and genetic evidence indicating that regulators of actin and microtubule dynamics are crucial for T cell activation and effector functions. In fact, the actin cytoskeleton participates in the initial clustering of TCR-major histocompatibility complex or peptide complexes, formation and stabilization of the immune synapse, integrin-mediated adhesion, and receptor sequestration, whereas both the actin and microtubule cytoskeletons regulate the establishment of cell polarity, cell migration, and directed secretion of cytokines and cytolytic granules. Over the past several years, we have begun to more thoroughly understand the contributions of specific actin-regulatory and actin-nucleating proteins that govern these processes. Herein, we discuss our current understanding of how activating receptors on T lymphocytes regulate the actin and microtubule cytoskeletons, and how in turn, these distinct but integrated cytoskeletal networks coordinate T cell immune responses.