CD8+ memory T-cell inflation renders compromised CD4+ T-cell-dependent CD8+ T-cell immunity via naïve T-cell anergy
نویسندگان
چکیده
Whether inflation of CD8+ memory T (mT) cells, which is often derived from repeated prime-boost vaccinations or chronic viral infections in the elderly, would affect late CD8+ T-cell immunity is a long-standing paradox. We have previously established an animal model with mT-cell inflation by transferring ConA-stimulated monoclonal CD8+ T cells derived from Ova-specific T-cell-receptor transgenic OTI mice into irradiation-induced lymphopenic B6 mice. In this study, we also established another two animal models with mT-cell inflation by transferring, 1) ConA-stimulated monoclonal CD8+ T cells derived from lymphocytic choriomeningitis virus glycoprotein-specific T-cell-receptor transgenic P14 mice, and 2) ConA-stimulated polyclonal CD8+ T cells derived from B6.1 mice into B6 mice with irradiation-induced lymphopenia. We vaccinated these mice with recombinant Ova-expressing Listeria monocytogenes and Ova-pulsed dendritic cells, which stimulated CD4+ T cell-independent and CD4+ T-cell-dependent CD8+ T-cell responses, respectively, and assessed Ova-specific CD8+ T-cell responses by flow cytometry. We found that Ova-specific CD8+ T-cell responses derived from the latter but not the former vaccination were significantly reduced in mice with CD8+ mT-cell inflation compared to wild-type B6 mice. We determined that naïve CD8+ T cells purified from splenocytes of mice with mT-cell inflation had defects in cell proliferation upon stimulation in vitro and in vivo and upregulated T-cell anergy-associated Itch and GRAIL molecules. Taken together, our data reveal that CD8+ mT-cell inflation renders compromised CD4+ T-cell-dependent CD8+ T-cell immunity via naïve T-cell anergy, and thus show promise for the design of efficient vaccines for elderly patients with CD8+ mT-cell inflation.
منابع مشابه
Multiple Myeloma Bone Marrow Mesenchymal Stromal Cells Inhibit CD8+ T Cell Function in a Process that May Implicate Fibroblast Activation Protein α
Background: Multiple myeloma (MM) is a malignant plasma cell proliferative disorder with limited immunotherapy treatment because of T cell dysfunction. Objective: To investigate the immunomodulatory function of bone marrow mesenchymal stromal cells (MM-BMSCs) on CD8+ T cells. Methods: Proliferation and cytotoxicity were detected by c...
متن کاملComparative Analysis of CD4+ and CD8+ T Cells in Tumor Tissues, Lymph Nodes and the Peripheral Blood from Patients with Breast Cancer
Background: CD4+ and CD8+ T cells are the main types of lymphocytes in cell-mediated immunity and play a central role in the induction of efficient immune responses against tumors. The frequencies of T cell subtypes in the peripheral blood and tumor tissues, and draining lymph nodes (dLN) can be considered as useful markers for evaluation of the immune system in cancers. Methods: In this study,...
متن کاملتعیین زیر جمعیت های لنفوسیت T و B و NK بکمک آنتی بادی های مونوکلونال در بیماران مبتلا به بیماری بهجت در ایران
Behcet disease (BD) is a systemic inflammatory disease of the unknown etiology. There is however, some evidence to suggest that immunological abnormalities are important in its pathogenesis, furthermore several T-cell abnormalities which may be quite relevant to autoimmune origin of the disease have been described. We report here our study of T-cell subsets, B and NK cells in 68 patients with B...
متن کاملEffects of Dietary Vitamin C, E and Fat on CD4 to CD8 T Cell Ratios in Peripheral Blood of Heat-stressed Broiler Chicks
متن کامل
Effect of ionizing radiation on development process of T-cell population lymphocytes in Chernobyl children
Background: The aim of preliminary study was determined development process status of T-cell population lymphocytes in Ukrainian children after 22 years from Chernobyl accident for next feasibility study. Material and Method: 150 participants aged 6 to 16 years are included in three groups: Group I (n=65), 30 to 60 km from center accident at zone 3th, Group II (n=65) 60 to 90 km from s...
متن کامل