Immunology

Here, we analyzed the phenotype and function of the human CD4+ T-cell subsets and lineages in paired resting lymph node and peripheral blood samples. Naive, central memory cells and effector memory cells as well as Th1, Th2, Th17 and Treg cells were equally represented in both compartments. On the other hand, cytotoxic CD4+ T cells were strikingly absent in the lymph nodes. CXCR5+CD4+ T cells, representing putative follicular Th (Tfh) cells were over-represented in lymph nodes and expressed higher levels of Tfh markers than their peripheral blood counterparts. Compared with the circulating pool, lymph-node-derived CXCR5+CD4+ T cells were superior in providing help to B cells. Thus, functionally competent Tfh cells accumulate in resting human lymph nodes, providing a swift induction of naive and memory antibody responses upon antigenic challenge.

physiology in lymph nodes

Here, we demonstrate that in contrast to blood and bone marrow Tregs, which showed a resting phenotype, the majority of CD4posCD25posCD127negFoxP3pos Tregs in secondary lymphoid organs were proliferating activated CD69posCD45RAneg cells with a hyperdemethylated FOXP3 gene and a broad T-cell receptor–Vβ repertoire, implying polyclonal activation. Activated CD69pos Tregs were distributed over both T-cell and B-cell areas, distant from Airepos and CD11cpos cells. In contrast to the anergic peripheral blood Tregs, lymphoid organ Tregs had significant ex vivo proliferative capacity and produced cytokines like interleukin-2, while revealing similar suppressive potential. Also, next to Treg-expressing chemokine receptors important for a prolonged stay in lymphoid organs, a significant part of the cells expressed peripheral tissue–associated, functional homing markers. In conclusion, our data suggest that human secondary lymphoid organs aid in the maintenance and regulation of Treg function and homeostasis

D Mathis lab and Tregs

TCRαβ+CD3+CD4−CD8−NK1.1− double negative (DN) Tregs comprise 1–3% of peripheral T lymphocytes in mice and humans. It has been demonstrated that DN Tregs can suppress allo-, xeno- and auto-immune responses in an Ag-specific fashion. However, the mechanisms by which DN Tregs regulate immune responses remain elusive. Whether DN Tregs can regulate DCs has not been investigated previously. In this study, we demonstrate that DN Tregs express a high level of CTLA4 and are able to down-regulate costimulatory molecules CD80 and CD86 expressed on Ag-expressing mature DCs (mDCs). DN Tregs from CTLA4 KO mice were not able to downregulate CD80 and CD86 expression, indicating that CTLA4 is critical for DN Treg-mediated downregulation of costimulatory molecule expression on Ag-expressing mature DCs. Furthermore, DN Tregs could kill both immature and mature allogeneic DCs, as well as Ag-loaded syngeneic DCs, in an Ag-specific manner in vitro and in vivo, mainly through the Fas-FasL pathway. These data demonstrate, for the first time, that DN Tregs are potent regulators of DCs and may have the potential to be developed as a novel immune suppression treatment.