DataSheet_1_Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation.docx

التفاصيل البيبلوغرافية
العنوان: DataSheet_1_Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation.docx
المؤلفون: Amy C. J. van der List (9343289), Nicolle H. R. Litjens (3181653), Mariska Klepper (3181656), Michiel G. H. Betjes (8407413)
سنة النشر: 2021
المجموعة: Smithsonian Institution: Digital Repository
مصطلحات موضوعية: Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, alloreactive, T-cells, kidney transplantation, antigen-specific, senescence
الوصف: Development of T-cell hyporesponsiveness to donor antigen may explain the substantial decreased risk for acute rejection in the years following kidney transplantation. The underlying mechanisms of donor-specific hyporesponsiveness (DSH) are largely unknown but may allow for lowering of immunosuppressive medication. Due to the onset of DSH being more rapid and pronounced in older recipients (+55 years), we hypothesized that immunosenescence/exhaustion of T lymphocytes would be a contributing factor. This study tested whether donor-reactive recipient T cells become hyporesponsive due to exhaustion from continuous stimulation by donor antigen. Circulating donor-reactive T cells of both young and elderly stable kidney transplant recipients (N=17) before and 3-5 years after transplantation were analyzed at the single cell level for expression of exhaustion markers by multi-parameter flow cytometry followed by unsupervised and unbiased clustering. Clusters containing cells of a particular expression profile with significant differential abundance after transplantation were identified and further analyzed. Unexpectedly, our results do not demonstrate an increase in exhausted donor antigen-reactive T cells post transplantation. Instead, we demonstrate a significant decrease in donor antigen-reactive CD4+ T cells expressing T cell immunoglobulin and ITIM domain (TIGIT) long after transplantation. Further analysis at earlier timepoints indicated that this decrease is already present at six months post transplantation. Characterization of these CD4+ T donor-reactive cells expressing TIGIT revealed them to have a predominantly central and effector memory T cell phenotype and a highly poly-functional cytokine expression profile. This study has therefore identified TIGIT as a marker for a previously undescribed polyfunctional donor-reactive CD4+ T cell population whose decline following kidney transplantation may explain development of DSH.
نوع الوثيقة: dataset
اللغة: unknown
Relation: https://figshare.com/articles/dataset/DataSheet_1_Expression_of_Senescence_Marker_TIGIT_Identifies_Polyfunctional_Donor-Reactive_CD4_T_Cells_Preferentially_Lost_After_Kidney_Transplantation_docx/14517132
DOI: 10.3389/fimmu.2021.656846.s001
الاتاحة: https://doi.org/10.3389/fimmu.2021.656846.s001
Rights: CC BY 4.0
رقم الانضمام: edsbas.6CC47E37
قاعدة البيانات: BASE
الوصف
DOI:10.3389/fimmu.2021.656846.s001