CD70 contributes to age-associated T cell defects and overwhelming inflammatory responses
Autor: | Yaxian Kong, Juan Du, Rui Song, Yongqin Zeng, Yangzi Song, Jiang Xiao, Yu Hao, Hui Zeng, Di Wang, Hong Zheng, Hongxin Zhao, Beibei Wang |
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Rok vydání: | 2020 |
Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Aging Adolescent Immunosenescence T cell Primary Cell Culture Apoptosis CD8-Positive T-Lymphocytes Biology Lymphocyte Activation medicine.disease_cause T cell aging Proinflammatory cytokine Young Adult Downregulation and upregulation medicine Humans Receptor Cells Cultured Aged Aged 80 and over Cell Biology Middle Aged Immune dysregulation Flow Cytometry Healthy Volunteers Up-Regulation CD70 medicine.anatomical_structure overwhelming inflammatory responses Immunology Female co-inhibitory molecules CD8 CD27 Ligand Research Paper |
Zdroj: | Aging (Albany NY) |
ISSN: | 1945-4589 |
Popis: | Aging is associated with immune dysregulation, especially T cell disorders, which result in increased susceptibility to various diseases. Previous studies have shown that loss of co-stimulatory receptors or accumulation of co-inhibitory molecules play important roles in T cell aging. In the present study, CD70, which was generally regarded as a costimulatory molecule, was found to be upregulated on CD4+ and CD8+ T cells of elderly individuals. Aged CD70+ T cells displayed a phenotype of over-activation, and expressed enhanced levels of numerous inhibitory receptors including PD-1, 2B4 and LAG-3. CD70+ T cells from elderly individuals exhibited increased susceptibility to apoptosis and high levels of inflammatory cytokines. Importantly, the functional dysregulation of CD70+ T cells associated with aging was reversed by blocking CD70. Collectively, this study demonstrated CD70 as a prominent regulator involved in immunosenescence, which led to defects and overwhelming inflammatory responses of T cells during aging. These findings provide a strong rationale for targeting CD70 to prevent dysregulation related to immunosenescence. |
Databáze: | OpenAIRE |
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