The Strategy of T Cell Antigen-presenting Cell Encounter in Antigen-draining Lymph Nodes Revealed by Imaging of Initial T Cell Activation

The development of an immune response critically relies on the encounter of rare antigen (Ag)-specific T cells with dendritic cells (DCs) presenting the relevant Ag. How two rare cells find each other in the midst of irrelevant other cells in lymph nodes (LNs) is unknown. Here we show that initial T cell activation clusters are generated near high endothelial venules (HEVs) in the outer paracortex of draining LNs by retention of Ag-specific T cells as they exit from HEVs. We further show that tissue-derived DCs preferentially home in the vicinity of HEVs, thus defining the site of cluster generation. At this location DCs efficiently scan all incoming T cells and selectively retain those specific for the major histocompatibility complex–peptide complexes the DCs present. Such strategic positioning of DCs on the entry route of T cells into the paracortex may foster T cell–DC encounter and thus optimize initial T cell activation in vivo

Mice lacking the MHC class II transactivator (CIITA) show tissue-specific impairment of MHC class II expression

CIITA activates the expression of multiple genes involved in antigen presentation and it is believed to be required for both constitutive and IFN\xce\xb3-inducible expression of these genes. To understand the role of CIITA in vivo, we have used gene targeting to generate mice that lack CIITA. CIITA-deficient (-/-) mice do not express conventional MHC class II molecules on the surface of splenic B cells and dendritic cells. In addition, macrophages resident in the peritoneal cavity do not express MHC class II molecules upon IFN\xce\xb3 stimulation nor do somatic tissues of mice injected with IFN\xce\xb3, in contrast with wild-type mice. The levels of li and H-2M gene transcripts are substantially decreased but not absent in CIITA (-/-) mice. The transcription of nonconventional MHC class II genes is, however, not affected by CIITA deficiency. A subset of thymic epithelial cells express MHC class II molecules. Nonetheless, very few mature CD4 T cells are present in the periphery of CIITA (-/-) mice despite MHC class II expression in the thymus. Consequently, CIITA (-/-) mice are impaired in T-dependent antigen responses and MHC class II-mediated allogeneic reponses

Thymus-specific serine protease contributes to the diversification of the functional endogenous CD4 T cell receptor repertoire

Thymus-specific serine protease expression in stromal as well as hematopoietic cells in the thymus is needed for diversification of the endogenous repertoire of TCRs specific for a particular protein antigen

Peut-on rendre des cellules cytotoxiques matures tolerantes

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Les cellules Th17

Après plus de 20 ans d’hégémonie, le paradigme Th1-Th2 a été ébranlé par la découverte d’une nouvelle population de cellules T CD4 effectrices, les cellules Th17. Ces cellules ont des propriétés pro-inflammatoires marquées et contrôlent les bactéries extracellulaires principalement à la surface des épithéliums. Les cellules Th17 sont aussi les effecteurs principaux de pathologies auto-immunes à spécifité d’organe - comme l’EAE (encéphalomyélite auto-immune expérimentale) - autrefois attribuées à des réponses Th1. La découverte des cellules Th17 confirme l’hypothèse d’une grande diversité des réponses T CD4 effectrices et indique que la régulation fine de ces différentes populations est essentielle au maintien de l’intégrité tissulaire

[Th17 cells, a novel proinflammatory effector CD4 T cell population.]

International audienceAfter more than 20 years of hegemony, the Th1-Th2 paradigm was recently shaken by the discovery of a novel population of CD4 effector T cells, the Th17 cells. Th17 effector cells produce IL-17 and IL-22 and thus have pro-inflammatory properties notably favoring neutrophils recruitment and thus control of extracellular bacteria mainly at the epithelium surface. Th17 cells appear also as the major inducer of organ specific autoimmune pathologies such as EAE or rheumatoid arthritis, a function previously attributed to Th1 effector cells. The discovery of Th17 cells further supports the notion that effector CD4 T cells responses are diverse in vivo and that fine tuning of these different effector cells is critical to maintain tissue integrity. double dagger

Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire

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