Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W Baltimore St., HSF1, Room 380, Baltimore, MD, 21201, USA.
Sci Rep. 2022 Nov 14;12(1):19487. doi: 10.1038/s41598-022-24126-4.
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.
外周 T 细胞表达多样化的抗原特异性受体,共同保护机体免受各种病原体的侵害。在这种情况下,记忆 T 细胞的总库对于清除病原体后长期维持至关重要。由于这些营养因子包括细胞因子和自身肽-MHC,两者均可从内源性抗原呈递细胞 (APC) 获得,因此我们假设,在体内增强 APC 的数量可能是扩增记忆 T 细胞群体的可行策略。我们通过用 FMS 样酪氨酸激酶 3 配体 (Flt3l) 急性处理完整小鼠来评估这一点,Flt3l 可促进 APC 的扩增。在这里,我们报告说,这种治疗方法可以扩增效应记忆 CD4+和 CD8+T 细胞,并增加其 KLRG1 和 CD25 的表达。在淋巴结和脾脏中,扩增仅限于特定的 CD8(CD44 低但 CD62L-)亚群。从功能上讲,该亚群与幼稚 T 细胞不同,在重新刺激时可以产生大量效应细胞因子。总之,这些数据表明,Flt3L 的给药可以影响完整外周免疫区室中 APC 的更新以及特定 CD8+T 细胞亚群的相应流动。