5 T cells into Foxp3+ Treg cells in the PLNs accumulating in the pancreatic islets. Furthermore, tolerogenic plasmacytoid DCs (pDCs) characterized by low MHC class II molecule expression and TGF-β production are critical in the PLNs for the recruitment of Treg

cells into the pancreatic islets by inducing CXCR3 expression. PI3K inhibitor Accordingly, pDC depletion in α-galactosylceramide-treated proinsulin 2−/− NOD mice abrogates the protection against T1D. These findings reveal that upon repetitive iNKT-cell stimulation, pDCs are critical for the recruitment of Treg cells in the pancreatic islets and the prevention of T1D development. “
“Immunoproteasomes containing the IFN-inducible subunits β1i (LMP2), β2i (MECL-1) and β5i (LMP7) alter proteasomal cleavage preference and optimize the generation of peptide ligands of MHC class I molecules. Here, we report on an unexpected new function of immunoproteasome subunits

for the survival and expansion of CD4+ and CD8+ T cells during viral infection of mice. The effect of immunoproteasome subunit deficiency on T-cell survival upon adoptive transfer was most prominent for the lack of LMP7 followed by MECL-1 and LMP2. The survival of T cells in uninfected mice or the homeostatic expansion after transfer into buy BAY 73-4506 RAG-2−/− mice was not affected by the lack of the immunosubunits. Lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cells lacking LMP7 or MECL-1 started to divide after transfer into LCMV-infected mice but experienced a considerable cell loss within 2 days after transfer. We provide strong evidence that the loss of immunoproteasome-deficient T cells after transfer is not a consequence of graft rejection by the host, but instead is based on the requirement for immunoproteasomes for the survival of T cells in LCMV-infected mice. Therefore, the immunoproteasome

may qualify as a potential new target for the suppression of undesired proinflammatory T-cell responses. The proteasome Selleck Fluorouracil core complex, referred to as 20S proteasome, is a cylinder-shaped structure consisting of 28 subunits, arranged in four stacked rings. The two outer rings, each made up of seven α-type subunits (α1–α7) are framing the two inner rings, each composed of seven β-type subunits (β1–β7). The catalytic activity is performed by three β-subunits of each inner ring: β1 (δ), β2 (MC14) and β5 (MB1). In the course of an immune response, the constitutive β-subunits are replaced in newly assembled proteasomes by the IFN-γ- and TNF-α-inducible subunits β1i (LMP2), β5i (LMP7) and β2i (MECL-1) 1, thereby building so-called immunoproteasomes 2. Immunoproteasomes cleave Ag with a different cleavage preference 3, 4, thus optimizing the quantity and quality of the generated peptides for presentation by MHC class I molecules 5–8.