Central Nervous System-Infiltrating T Lymphocytes in Stroke Are Activated via Their TCR (T-Cell Receptor) but Lack CD25 Expression
| Autor: | Alexander Dressel, Juliane Gellrich, Michael Kirsch, Antje Vogelgesang, Juliane Schulze |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
CD4-Positive T-Lymphocytes
Central Nervous System Male Central nervous system Programmed Cell Death 1 Receptor Receptors Antigen T-Cell Brain damage Lymphocyte Activation T-Lymphocytes Regulatory 03 medical and health sciences 0302 clinical medicine Medicine Humans Middle cerebral artery occlusion IL-2 receptor Stroke Aged Advanced and Specialized Nursing Aged 80 and over business.industry T-cell receptor Interleukin-2 Receptor alpha Subunit Middle Aged medicine.disease T-lymphocyte activation medicine.anatomical_structure Cancer research Female Neurology (clinical) medicine.symptom Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery 030215 immunology |
| Zdroj: | Stroke. 52(9) |
| ISSN: | 1524-4628 |
| Popis: | Background and Purpose: T lymphocytes contribute to secondary brain damage after stroke. It has not been fully investigated whether this contribution is caused by antigen-specific or antigen-nonspecific activation of T lymphocytes. Lymphocytes from Nur77 GFP transgenic mice express a fluorescent protein upon activation via the TCR (T-cell receptor), allowing the differentiation of activation mode in a natural repertoire of immune cells and antigens. Methods: Middle cerebral artery occlusion or sham surgery was performed, and T-lymphocyte activation was analyzed by flow cytometry in the brain, spleen, and blood 16 hours, 2 days, 3 days, 4 days, and 7 days after surgery. Results: Ipsilateral hemispheric T-lymphocyte invasion peaked on day 4 poststroke. Here, we observed PD-1 (programmed cell death protein 1) expression on almost all invading T lymphocytes, while CD25 expression was low. CD25+, CD69+, or PD-1+ T lymphocytes predominantly displayed antigen-specific activation; the opposite was observed for T lymphocytes isolated from the blood. A mixed activation that favored antigen-specific activation was observed in the spleen. PD-1 was upregulated within the brain, whereas CD25 was not. Antigen-specific T lymphocytes home to the brain, while antigen-nonspecifically activated cells remain within the blood. Conclusions: Our data clearly demonstrate antigen-specific activation of T lymphocytes infiltrating ischemic brain lesions in stroke. The high expression of inhibitory PD-1 and low expression of CD25 on activated T lymphocytes in the brain most likely reflect immunosuppressive mechanisms. |
| Databáze: | OpenAIRE |
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