Acute effects of FLT3L treatment on T cells in intact mice

Abstract

Peripheral T cells express a diverse repertoire of antigen-specific receptors, which together protect against the full range of pathogens. In this context, the total repertoire of memory T cells which are maintained by trophic signals, long after pathogen clearance, is critical. Since these trophic factors include cytokines and self-peptide-MHC, both of which are available from endogenous antigen-presenting cells (APC), we hypothesized that enhancing APC numbers in vivo can be a viable strategy to amplify the population of memory T cells. We evaluated this by acutely treating intact mice with FMS-like tyrosine kinase 3 ligand (Flt3l), which promotes expansion of APCs. Here we report that this treatment allowed for, an expansion of effector-memory CD4+ and CD8+ T cells as well as an increase in their expression of KLRG1 and CD25. In the lymph nodes and spleen, the expansion was limited to a specific CD8 (CD44-low but CD62L−) subset. Functionally, this subset is distinct from naïve T cells and could produce significant amounts of effector cytokines upon restimulation. Taken together, these data suggest that the administration of Flt3L can impact both APC turnover as well as a corresponding flux of specific subsets of CD8+ T cells in an intact peripheral immune compartment.