TCRαβ(+) CD4(-)CD8(-)NK(-) double negative T cells (DN T cells) can act as regulatory T cells to inhibit allograft rejection and autoimmunity. Their role in graft-versus-host disease and mechanisms of suppression remain elusive. In this study, we demonstrate that DN T cells can inhibit CD4(+) T cell-mediated GVHD in a semi-allogeneic model of bone marrow transplantation. Furthermore, we present evidence of a novel autocrine IFNγ signaling pathway in Fas-deficient C57BL/6.lpr (B6.lpr) DN T cells. B6.lpr DN T cells lacking IFNγ or its receptor were impaired in their ability to suppress syngeneic CD4(+) T cells responding to alloantigen stimulation both in vitro and in vivo. Autocrine IFNγ signaling was required for sustained B6.lpr DN T cell IFNγ secretion in vivo and for upregulation of surface Fas ligand expression during TCR stimulation. Fas ligand (FasL) expression by B6.lpr DN T cells permitted lysis of activated CD4(+) T cells and was required for suppression of GVHD. Collectively, our data indicate that DN T cells can inhibit GVHD and that IFNγ plays a critical autocrine role in controlling the regulatory function of B6.lpr DN T cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471870 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047732 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
The atypical chemokine receptor 2 reduces T cell expansion and tertiary lymphoid tissue but does not limit autoimmune organ injury in lupus-prone B6lpr mice.
Front Immunol
May 2024
Division of Nephrology, Department of Medicine IV, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Introduction: The atypical chemokine receptor 2 (ACKR2) is a chemokine scavenger receptor, which limits inflammation and organ damage in several experimental disease models including kidney diseases. However, potential roles of ACKR2 in reducing inflammation and tissue injury in autoimmune disorders like systemic lupus erythematosus (SLE) and lupus nephritis are unknown, as well as its effects on systemic autoimmunity.
Methods: To characterize functional roles of ACKR2 in SLE, genetic Ackr2 deficiency was introduced into lupus-prone C57BL/6lpr (Ackr2-/- B6lpr) mice.
Egr2 Deletion in Autoimmune-Prone C57BL6/lpr Mice Suppresses the Expression of Methylation-Sensitive Dlk1-Dio3 Cluster MicroRNAs.
Immunohorizons
December 2023
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA.
We previously demonstrated that the upregulation of microRNAs (miRNAs) at the genomic imprinted Dlk1-Dio3 locus in murine lupus is correlated with global DNA hypomethylation. We now report that the Dlk1-Dio3 genomic region in CD4+ T cells of MRL/lpr mice is hypomethylated, linking it to increased Dlk1-Dio3 miRNA expression. We evaluated the gene expression of methylating enzymes, DNA methyltransferases (DNMTs), and demethylating ten-eleven translocation proteins (TETs) to elucidate the molecular basis of DNA hypomethylation in lupus CD4+ T cells.
View Article and Find Full Text PDFdeficiency alters gut microbiota and ameliorates -mediated systemic autoimmunity in male mice.
Front Immunol
March 2023
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
NLRP12 has dual roles in shaping inflammation. We hypothesized that NLRP12 would modulate myeloid cells and T cell function to control systemic autoimmunity. Contrary to our hypothesis, the deficiency of in autoimmune-prone B6.
View Article and Find Full Text PDFP2X7 purinergic receptor plays a critical role in maintaining T-cell homeostasis and preventing lupus pathogenesis.
Front Immunol
October 2022
UMR 996, INSERM, Université Paris-Saclay, Clamart, France.
The severe lymphoproliferative and lupus diseases developed by MRL/ mice depend on interactions between the Fas mutation and MRL genetic background. Thus, the Fas mutation causes limited disease in C57BL/6 mice. We previously found that accumulating B220 CD4CD8 double negative (DN) T cells in MRL/ mice show defective P2X7 receptor ( P2X7)-induced cellular functions, suggesting that P2X7 contributes to T-cell homeostasis, along with Fas.
View Article and Find Full Text PDFImmunohistochemistry of Immune Cells and Cells Bound to Administered Antibodies in Liver, Lung, Pancreas, and Colon of B6/lpr Mice.
Bio Protoc
July 2022
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
Employing a novel mouse model of immune related adverse events (irAEs) induced by combination of anti-PD1 and anti-CTLA-4 antibodies, we visualized immune infiltration into the liver, lung, pancreas, and colon. Here, we describe the avidin-biotin conjugate (ABC) method used to stain T cells (CD4 and CD8), B cells (CD19), macrophages (F4/80), and cells bound by the administered rat anti-mouse antibodies for chromogenic immunohistochemistry (IHC). Using a biotinylated goat anti-rat antibody, we detected the localization of cells bound to the antibodies for PD-1 and CTLA-4.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!