Proliferative arrest and cell cycle regulation in CD8+CD28− versus CD8+CD28+ T cells
| Autor: | Urban J. Scheuring, Argyrios N. Theofilopoulos, Helen Sabzevari |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cell type
CD8 Antigens Immunology Receptors Antigen T-Cell chemical and pharmacologic phenomena Lymphocyte Activation Flow cytometry CD28 Antigens T-Lymphocyte Subsets Cyclin-dependent kinase medicine Humans Immunology and Allergy IL-2 receptor Phosphorylation Cyclin-Dependent Kinase Inhibitor p16 medicine.diagnostic_test biology Cell Cycle T-cell receptor Membrane Proteins CD28 hemic and immune systems General Medicine Middle Aged Cell cycle Cell biology biology.protein Leukocyte Common Antigens CD8 |
| Zdroj: | Human Immunology. 63:1000-1009 |
| ISSN: | 0198-8859 |
| DOI: | 10.1016/s0198-8859(02)00683-3 |
| Popis: | CD8 + CD28 − T cells have been characterized by oligoclonal expansions, impaired proliferative responses, but preserved cytotoxicity and reduced telomeres. To examine this subset further and define the underlying mechanisms of proliferation arrest, we investigated several features of this cell type compared with CD8 + CD28 + controls. We analyzed expression of various activation markers, thymidine incorporation upon activation, T-cell receptor (TCR) ζ-chain phosphorylation, cell cycle characteristics, and cell cycle related gene expression. Flow cytometry revealed higher expression of CD11b, CD29, CD57, and CD94, and lower expression of CD25 in CD8 + CD28 − compared with CD8 + CD28 + T cells. Sorted CD8 + CD16 − CD28 − cells exhibited decreased phosphorylation of the TCR ζ-chain in three of four probands. Proliferation of these T cells was impaired, even when activated with mitogens that bypass TCR signaling. Cell cycle profiles demonstrated a lower percentage of cycling cells and significantly higher levels of cyclin dependent kinase inhibitor p16 INK4a in the CD28 − subset compared with the CD28 + control. These observations suggest that expanded CD8 + CD28 − T cells in normal elderly individuals have reduced proliferation concomitant with increased p16 INK4a expression. Defects in TCR signaling were associated with altered TCR ζ-chain phosphorylation. |
| Databáze: | OpenAIRE |
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