Characterization with age of resident T cells within secondary lymphoid organs in the steady state

Using two different experimental approaches, we here highlight the long-term residence of a substantial proportion of CD4 Treg and CD4 Tmem cells within the secondary lymphoid organs of specific pathogen-free mice. Microbiota plays an important role in T-cell residence in Peyer’s patches, but only a minor one, if any, in lymph nodes. Lymph node-resident CD4 Treg and CD4 Tmem cells share many phenotypic and functional characteristics, including a core transcriptional profile, with their cell-counterparts from non-lymphoid tissues. In particular, S1PR1 down-regulation may represent the main mechanism accounting for T-cell residency within secondary lymphoid organs. Strikingly, T-cell residence increases with age, to the point that the majority of CD4 Treg and Tmem cells from lymph nodes are in fact, resident T cells in old mice. Altogether, our results show that T-cell residence is not only a hallmark of non-lymphoid tissues, but can be extended to secondary lymphoid organs. CD4 T cells from lymph nodes (peripheral + mesenteric) of C57BL/6 Foxp3-GFP mice treated or not with anti-LFA-1 and anti-VLA-4 antibodies 2 days before were purified by using Dynabeads Untouched Mouse CD4 Cells Kit (Invitrogen). Then, CD4 Treg and Tmem cells were flow-cytometry sorted as CD4+ CD8α- TCRβ+ GFP+ for Treg and CD4+ CD8α- TCRβ+ GFP- CD44hi for Tmem using a FACS-ARIA3 flow cytometer.