LNSCs present peptide–MHCII complexes acquired from DCs to CD4+ T cells and induce T cell dysfunction by preventing their proliferation and survival.

Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from nonulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4+ and of CD68+ cells were slightly higher in L-CL, a five-fold increase of CD8+ cells was observed in L-CL, as compared to E-CL. Moreover, CD8+ T-cells from L-CL expressed significantly higher levels of granzymeA than E-CL. Interestingly, granzymeA expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-γ + and IL-10+ cells were higher in L-CL as compared to E-CL, with CD4+ T-cells and CD68+ monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8+granzymeA+ T-cells is involved in lesion progression in human CL.

MHCII-restricted antigen presentation by lymph node stromal cells is essential for regulatory T-cell proliferation and functions, and for the regulation of autoimmunity.

Plasmacytoid dendritic cells (pDCs) have been shown to both mediate and prevent autoimmunity, and the regulation of their immunogenic versus tolerogenic functions remains incompletely understood. Here we demonstrate that, compared to other cells, pDCs are the major expressors of Indoleamine-2,3-dioxygenase (IDO) in steady-state lymph nodes (LNs). IDO expression by LN pDCs was closely dependent on MHCII-mediated, antigen-dependent, interactions with Treg. We further established that IDO production by pDCs was necessary to confer suppressive function to Tregs. During EAE development, IDO expression by pDCs was required for the generation of Tregs capable of dampening the priming of encephalitogenic T cell and disease severity. Thus, we describe a novel crosstalk between pDCs and Tregs: Tregs shape tolerogenic functions of pDCs prior to inflammation, such that pDCs in turn, promote Treg suppressive functions during autoimmunity.

Lymphatic endothelial cells (LECs) chemoattract naïve T cells and promote their survival in the lymph nodes, and can cross-present antigens to naïve CD8 + T cells to drive their proliferation despite lacking key costimulatory molecules. However, the functional consequence of LEC priming of CD8 + T cells is unknown. Here, we show that while many proliferating LECeducated T cells enter early apoptosis, the remainders comprise a long-lived memory subset, with transcriptional, metabolic, and phenotypic features of central memory and stem cell-like memory T cells. In vivo, these memory cells preferentially home to lymph nodes and display rapid proliferation and effector differentiation following memory recall, and can protect mice against a subsequent bacterial infection. These findings introduce a new immunomodulatory role for LECs in directly generating a memory-like subset of quiescent yet antigenexperienced CD8 + T cells that are long-lived and can rapidly differentiate into effector cells upon inflammatory antigenic challenge.