![]() ![]() In addition to the well-characterized FOXP3 + Treg cell subset, a number of other IL-10-producing but FOXP3 –CD25 – and phenotypically heterogeneous subsets of Treg cells with low IL-4 secretion capacity (often referred to as T regulatory type-1, TR1 cells) have been described. Interleukin-10 (IL-10)-producing regulatory T cells (Tregs) play a central role in the maintenance of normal immune homeostasis, and dysregulation of Treg cell development and/or function plays roles both in the development of autoimmune disease and in the progression of cancer. Thus, TFH cells can differentiate into TR1 cells in vivo, and BLIMP1 is a gatekeeper of this cellular reprogramming event. Bcl6 and Prdm1 are also necessary for anti-CD3 mAb-induced TR1 formation. In contrast, deletion of Prdm1 selectively abrogates the TFH-to-TR1 conversion. Furthermore, pMHCII-NPs trigger cognate TR1 cell formation in TFH cell-transfused immunodeficient hosts, and T-cell-specific deletion of Bcl6 or Irf4 blunts both the TFH expansion and TR1 formation induced by pMHCII-NPs. Pseudotime analyses of scRNAseq data and multidimensional mass cytometry revealed progressive downregulation and upregulation of TFH and TR1 markers, respectively. ![]() Here, we show that the peptide-major histocompatibility complex class II (pMHCII) monospecific immunoregulatory T-cell pools that arise in vivo in different genetic backgrounds in response to pMHCII-coated nanoparticles (pMHCII-NPs) are invariably comprised of oligoclonal subpools of T follicular helper (TFH) and TR1 cells with a nearly identical clonotypic composition but different functional properties and transcription factor expression profiles. The identities of the progenitor(s) and transcriptional regulators of this T-cell subset remain unclear. Chronic antigenic stimulation can trigger the differentiation of antigen-experienced CD4 + T cells into T regulatory type 1 (TR1) cells, a subset of interleukin-10-producing Treg cells that do not express FOXP3. ![]()
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