Project description:This SuperSeries is composed of the following subset Series: GSE26714: Expression data from Tregs adoptively transferred in MHC II competent or deficient recipients GSE27151: Expression data from Tregs purified from WT-CD3KO or IIKO-CD3KO chimeras Refer to individual Series
Project description:Disruption of TCR /MHC class II interactions leads rapidly to alterations of the common CD4 Treg transcriptional signature Self-deprived, non-functional Tregs were compare to fully functional Tregs by microarrays. Total T cells from the periphery of WT mice were adoptively transferred into CD3ε-/- recipient mice lacking or not MHC class II molecule expression (MHC II- or MHC II+ recipient mice, respectively). Five days later, peripheral Tregs transferred in MHC II - competent (CD4CD25B6) or - deficient (CD4CD25IIko) recipient were purified for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Th1 cells were adoptively transferred into RAG1 KO mice from either wildtype (Il23rwt/eGFP) or KO (Il23reGFP/eGFP) donors. At the peak of disease in recipients of wildtype cells, the animals were euthanized and intestinal T cells were isolated from the chosen recipients of both wildtype and KO cells for 10x massively parallel single-cell RNA-sequencing.
Project description:We used immunocompetent Fah-/- mice as the recipients and adoptively transferred HBsAg+ hepatocytes from HBs-Tg mice to replace the recipient hepatocytes (HBs-HepR). HBs-HepR mice maintained persistent HBsAg expression with chronic hepatitis and spontaneous liver fibrosis, and eventually developed HCC with a prevalence of 100%.
Project description:We used immunocompetent Fah-/- mice as the recipients and adoptively transferred HBsAg+ hepatocytes from HBs-Tg mice to replace the recipient hepatocytes (HBs-HepR). HBs-HepR mice maintained persistent HBsAg expression with chronic hepatitis and spontaneous liver fibrosis, and eventually developed HCC with a prevalence of 100%.
Project description:The T cell response to Chlamydia genital tract infections in humans and mice is unusual in that the majority of antigen-specific CD8 T cells are not restricted by HLA/MHC class I and therefore have been referred to as “unrestricted” or “atypical”. We previously reported that a subset of unrestricted murine Chlamydia-specific CD8 T cells had an unusual cytokine polarization pattern that included IFN-ɣ and IL-13. For this report, we investigated the transcriptome of Chlamydia-specific CD8ɣ13 T cells, comparing them to Chlamydia-specific multifunctional Tc1 clones using gene expression micro array analysis. The molecular study revealed that CD8ɣ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clone and CD8ɣ13 T cell clones to determine whether either influenced bacterial clearance or immunopathology during Chlamydia muridarum (Cm) genital tract infections. To our surprise, an adoptively transferred CD8ɣ13 T cell clone was remarkably proficient at preventing chlamydia immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly protect from immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published Chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation or deplete the CD4 T cell compartment.
Project description:In this experiment, the gene expression of CD8+ T cells primed in the presence or absence of Tregs on a single cell level was analyzed. For this purpose, Ly5.1 OT-I T cells were adoptively transferred into Treg deficient (DEREG+) or Treg replete (DEREG-) mice, activated with DC-OVA, isolated after 3 days, and analyzed by scRNAseq. Invididual samples were indexed with oligo-tagged TotalSeq-C antibodies and pooled prior to the analysis. We observed that Tregs reduced the expression of IL-2 responsive genes, including key cytotoxic molecule granzyme B. Unsupervised clustering revealed 5 clusters including a cluster of cells which did not match any usual CD8+ subsets and, due to unusual co-expression of effector molecules such as GZMK and KLRK1, were dubbed super-effector cells.
Project description:Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titrable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models. Global HDAC11 deletion had no effect on health or development, and compared to WT controls, Foxp3+ Tregs lacking HDAC11 showed increased suppressive function, and increased expression of Foxp3 and TGF-beta. Likewise, compared to WT recipients, conditional deletion of HDAC11 within Tregs led to long-term survival of fully MHC-mismatched cardiac allografts, and prevented development of transplant arteriosclerosis in an MHC class II-mismatched allograft model. The translational significance of HDAC11 targeting was shown by the ability of an HDAC11i to promote long-term allograft allografts in fully MHC-disparate strains. These data are powerful stimuli for the further development and testing of HDAC11-selective pharmacologic inhibitors, and may ultimately provide new therapies for transplantation and autoimmune diseases.
Project description:To fine map the continuum of molecular changes that occur as B cells differentiate to antibody secreting plasma cells in response to the T cell independent antigens LPS and NP-Ficoll we performed scRNA-seq. WT or IRF4-deficient B cells were CTV labeled and adoptively transferred into congenically disparate uMT hosts. One day later, the mice were innoculated with LPS and all transferred cells isolated at 72 hours and profiled on the 10x Genomimcs 5' Library Kit. In addition, we adoptively transferred WT B cells into congenically disparate WT hosts and innoculated the animals with either LPS or NP-Ficoll, and 72 hours later performed scRNA-seq on all responding B cells.