Tatsumi et al. showed that CD301b+ migratory cDC2s were required and sufficient to amass B and T cells in dLN of soluble antigen-immunized mice and, via an antigen-independent MHC-II/TCR-reliant process, to transiently retain and upregulate CD69 on naive polyclonal CD4+ T cells newly arrived in LNs. CD62L blockade and FTY720 treatment of mice, which disrupted CD301b+ DC positioning at LN HEVs, showed that these DCs immediately and directly presented antigens to activate scarce CD4+ T cell cognate clones, optimally primed and expanded the antigen-specific CD4+ T cells for primary and memory responses, and promoted TH2 differentiation.
Contributed by Paula Hochman
ABSTRACT: During the initiation of adaptive immune responses, millions of lymphocytes must be scanned to find the few cognate clones. The activation mechanisms of CD4 T cells have been extensively studied, but the cellular mechanisms that drive selection of cognate clones are not completely understood. Here, we show that recently homed naïve polyclonal CD4 T cells are temporarily retained before leaving the lymph node. This stop-and-go traffic of CD4 T cells provides an adequate time window for efficient scanning and timely priming of antigen-specific cognate clones. CD301b+ DCs, a major subset of migratory cDC2 cells, localize to the areas around high endothelial venules, where they retain incoming polyclonal CD4 T cells through MHCII-dependent but antigen-independent mechanisms, while concurrently providing cognate stimuli for priming. These results indicate that CD301b+ DCs function as an immunological “display window” for CD4 T cells to efficiently scan their antigen specificity.
Author Info: (1) Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA. (2) Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jer
Author Info: (1) Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA. (2) Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
