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:We used microarrays to determine how the quality and quantity of peptide-MHC impact TCR-induced gene expression in vivo. Adoptively transferred 5CC7 T cells were stimulated in vivo with different doses if two peptides: MCC peptide is a strong agonist and 102S peptide is a weak agonist for the 5CC7 TCR. After 48hours later, T cells were purified and gene expression was assessed using microarray.