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CD4 T cells share common developmental pathways with CD8 T cells, and upon maturation, CD4 T conventional T (Tconv) cells lack phenotypic markers that distinguish these cells from FoxP3 T regulatory cells. We developed a tamoxifen-inducible ThPOK line with Frt sites inserted on either side of the CreERT2-hCD2 cassette, and a Foxp3 strain, expressing Ametrine and FlpO in Foxp3 cells. Breeding these mice resulted in a CD4conv line that allows for the specific manipulation of a gene in CD4 Tconv cells. As FlpO removes the CreERT2-hCD2 cassette, CD4 Treg cells are spared from Cre activity, which we refer to as allele conditioning. Comparison with an E8I mouse that enables inducible targeting of CD8 T cells, and deletion of two inhibitory receptors, PD-1 and LAG-3, in a melanoma model, support the fidelity of these lines. These engineered mouse strains present a resource for the temporal manipulation of genes in CD4 T cells and CD4 Tconv cells.
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http://dx.doi.org/10.1016/j.immuni.2021.08.029 | DOI Listing |
Diabetes Metab Res Rev
September 2025
Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK.
Abatacept is a CTLA4-Ig fusion protein that blocks CD80/CD86-dependent T-cell co-stimulation. When administered, Abatacept limits, to a variable degree, loss of stimulated C-peptide secretion in patients with newly-diagnosed type 1 diabetes (T1D), while reducing both circulating memory CD4 T-cells and T follicular helper (Tfh) cells; however, its precise mechanism of action is not known. To investigate this effect, we studied 12 patients, using multi-parameter flow cytometry, who each self-administered Abatacept in subcutaneous formulation for 6 months within 100 days of diagnosis.
View Article and Find Full Text PDFbioRxiv
July 2025
Section of Transplantation, Department of Surgery, The University of Chicago, 60637.
Transplantation tolerance without the need for lifelong immunosuppression is a central goal in transplant immunology yet prior sensitization events remain a major barrier to achieving stable tolerance. In reproductive immunology by contrast, pregnancy represents a spontaneous model of tolerance where the semi-allogeneic fetus evades rejection even in multiparous or previously sensitized mothers. CD8 T cell phenotypes of tolerance and rejection have been previously reported in transplant and pregnancy, but the transcriptional states of donor and fetus-specific CD4 T cells remain poorly defined.
View Article and Find Full Text PDFUnlabelled: Cancer cells frequently lose MHC I to evade CD8 T cell recognition. While Natural Killer (NK) cells are poised to target MHC I-deficient cancer cells, MHC I loss alone is often insufficient to unleash fully effective NK cell responses. Here we show that selective intra-tumoral (IT) ablation of regulatory T (Treg) cells elicited potent antitumor NK cell responses that controlled MHC I-deficient and even MHC I cancers.
View Article and Find Full Text PDFFront Immunol
July 2025
Diabetes Research Institute, Division of Immunology, Transplantation and Infectious Diseases (DITID), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Introduction: Secondary and tertiary lymphoid structures are a critical target of suppression in many autoimmune disorders, protein replacement therapies, and in transplantation. Although antigen-specific regulatory T cells (Tregs), such as chimeric antigen receptor (CAR) Tregs, generally persist longer and localize to target tissues more effectively than polyclonal Tregs in animal models, their numbers still progressively decline over time. A potential approach to maximize Treg activity in vivo is the expression of chemokine receptors such as CXCR5, which would enable localization of a greater number of engineered cells at sites of antigen presentation.
View Article and Find Full Text PDFFront Immunol
July 2025
Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Background: () is a zinc finger transcription factor gene that regulates gene expression by recognizing and binding to specific DNA sequences. Preliminary studies have suggested that plays a pivotal role in the invasion and metastasis of various solid cancers. However, its role within the tumor immune microenvironment, as well as its prognostic value and potential for predicting responses to immunotherapy across different cancer types, remains inadequately explored and warrants a comprehensive systematic analysis.
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