Trends Immunol. 2026 Mar 7:S1471-4906(26)00035-9. doi: 10.1016/j.it.2026.02.004. Online ahead of print.
ABSTRACT
CD8+ T cell migration is central to host defense, enabling clonal selection, tissue infiltration, and elimination of infected cells. While chemokines guide these cells by activating Rac for F-actin polymerization, recent studies reveal a complementary mechanism through Rho activation. This pathway relies on tissue confinement, which deforms the nucleus, activates the actomyosin network, and allows CD8+ T cells to use physical cues for surveillance without external signals. In this review article, we explore how chemokine- and mechanosensing-dependent pathways guide CD8+ T cell surveillance and introduce a ‘front-‘ versus ‘rear-driven’ motility model to illustrate their integration for effective tissue monitoring. Ultimately, the interplay of biochemical and physical cues ensures tissue-specific protection by T cells during homeostasis and inflammation.
PMID:41796457 | DOI:10.1016/j.it.2026.02.004