Biology subjects

Lambert-Emo, K.

Publications and source records attributed to Lambert-Emo, K..

2 recordsLinked to original sources

bioRxiv2020

TRM Integrins CD103 and CD49a Differentially Support Adherence and Motility After Resolution of Influenza Virus Infection

Tissue resident memory CD8 T (TRM) cells are a unique immune memory subset that develops and remains in peripheral tissues at the site of infection, providing future host resistance upon re-exposure to that pathogen. In the pulmonary system, TRM are identified through S1P antagonist CD69 and expression of integrins CD103/{beta}7 and CD49a/CD29({beta}1). Contrary to the established role of CD69 on CD8 T cells, the functions of CD103 and CD49a on this population are not well defined. This study examines the expression patterns and functions of CD103 and CD49a with a specific focus on their impact on T cell motility during influenza virus infection. We show that the TRM cell surface phenotype develops by two-weeks post-infection and that each integrin contributes a distinct function regulating CD8 T cell motility both in vitro and in vivo, with CD49a facilitating migration and CD103 limiting motility through tethering. These results demonstrate for the first time how CD103 and CD49a differentially impact adherence and migration in the tissue, likely affecting overall retention, maintenance of TRM, and host protection. Significance StatementCurrent influenza vaccination strategies require annual immunizations, with fairly low efficacy rates. One technique to improve protection against a greater breadth of influenza viruses is to elicit broadly cross-reactive cell-mediated immunity and generate a local population of cytotoxic T cells to respond to conserved regions of circulating viruses. However, this approach requires improved understanding of how these cells migrate within and attach to the tissue, in order to persist and offer long-term immunity. This study investigates how receptors on the T cell surface impact the cells ability to interact with the tissue and provide evidence for which of these receptors are essential for protection. Furthermore, these studies reveal functional in vivo mechanisms of cellular markers used to characterize TRM.

immunology↗

bioRxiv2019

Antigen and G-Protein Coupled Receptor signaling differentially control CD8 T cell motility immediately before and after virus clearance in a primary infection

In mice, experimental influenza virus infection stimulates CD8 T cell infiltration of the airways. Virus is cleared by day 9, and between days 8 and 9 there is an abrupt change in CD8 T cell motility behavior transitioning from low velocity and high confinement on day 8, to high velocity with continued confinement on day 9. We hypothesized that it is loss of virus and/or antigen signals in the context of high chemokine levels that drives the T cells into a rapid surveillance mode. Virus infection induces chemokine production, which may change when the virus is cleared. We therefore sought to examine this period of rapid changes to the T cell environment in the tissue and seek evidence on the roles of peptide-MHC and chemokine receptor interactions. Experiments were performed to block G protein coupled receptor (GPCR) signaling with Pertussis toxin (Ptx). Ptx treatment generally reduced cell velocities and mildly increased confinement, except on day 8 when velocity increased and confinement was relieved, suggesting chemokine mediated arrest. Blocking specific peptide-MHC with monoclonal antibody unexpectedly decreased velocities on days 7 through 9, suggesting TCR/peptide-MHC interactions promote cell mobility in the tissue. Together, these results suggest the T cells are engaged with antigen bearing and chemokine producing cells that affect motility in ways that vary with the day after infection. The increase in velocities on day 9 were reversed by addition of specific peptide, consistent with the idea that antigen signals become limiting on day 9 compared to earlier time points. Thus, antigen and chemokine signals act to alternately promote and restrict CD8 T cell motility until the point of virus clearance, suggesting the switch in motility behavior on day 9 may be due to a combination of limiting antigen in the presence of high chemokine signals as the virus is cleared.

immunology↗