Homeostatic regulatory T cell trafficking in peripheral lymph nodes (LYM2P.731)

Abstract

Abstract Regulatory T cells (Tregs) express the canonical marker Foxp3 and are critical for suppressing the immune response in homeostatic and inflammatory conditions. As widely studied as CD4+Foxp3+ Tregs are in mice, their physiologic trafficking and scanning behavior of antigen-presenting cells in secondary lymphoid organs (SLOs) have yet to be quantitatively analyzed. Our laboratory has previously described the dynamics of naïve T cell trafficking through SLOs and scanning of dendritic cells, revealing that CD4+ T cells and CD8+ T cells have distinct dynamic behaviors in the lymph node (LN). On average, CD4+ T cells spend less time scanning for self-peptide/MHC (self-pMHC), dwell shorter in LNs, and egress faster compared to CD8+ T cells. In this study, we use flow cytometry and 2-photon laser scanning microscopy to quantitate the trafficking kinetics and surveillance strategy of naïve Tregs in C57BL/6 mice LNs and to compare their behavior to conventional T cells. Our data reveal differences in naïve Treg trafficking in mesenteric versus other peripheral LNs. We also show that self-pMHC recognition regulates the scanning behavior and localization of Tregs in peripheral LNs. In addition, we describe a novel imaging platform for high-resolution intravital microscopy of T cell behavior within mesenteric LNs. These results add to mounting evidence that self-pMHC interactions dynamically control physiologic Treg retainment and contact-dependent suppressive function in peripheral LNs.