Regulatory T cells modulate inflammation and reduce infarct volume in experimental brain ischaemia

• Published in: Journal of cellular and molecular medicine 2014-08, Vol.18 (8), p.1571-1579
• Main Authors: Brea, David, Agulla, Jesús, Rodríguez‐Yáñez, Manuel, Barral, David, Ramos‐Cabrer, Pedro, Campos, Francisco, Almeida, Angeles, Dávalos, Antoni, Castillo, José
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Angiogenesis; Animals; Blotting, Western; Brain; Brain Ischemia - etiology; Brain Ischemia - immunology; Brain Ischemia - prevention & control; Brain research; CD11b antigen; CD28 antigen; CD4 antigen; Cell Proliferation; Cells, Cultured; cerebrovascular disease/stroke; Cloning; Cytokines - metabolism; Enzyme-Linked Immunosorbent Assay; Experiments; Flow Cytometry; Foxp3 protein; Immunoenzyme Techniques; immunomodulation; Immunoregulation; Immunosuppressive Agents; Infarction, Middle Cerebral Artery - etiology; Infarction, Middle Cerebral Artery - immunology; Infarction, Middle Cerebral Artery - prevention & control; Inflammation; Inflammation - immunology; Inflammation - pathology; Inflammatory response; Ischemia; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Magnetic Resonance Imaging; Male; Neovascularization, Pathologic - immunology; Neural cell adhesion molecule; Neural Stem Cells - immunology; Neural Stem Cells - pathology; Neurogenesis; NMR; Nuclear magnetic resonance; Original; Rats; Rats, Sprague-Dawley; regulatory T cells; Stroke; Stroke - etiology; Stroke - immunology; Stroke - prevention & control; Studies; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Tumor necrosis factor-TNF
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12304

Brain ischaemia (stroke) triggers an intense inflammatory response predominately mediated by the accumulation of inflammatory cells and mediators in the ischaemic brain. In this context, regulatory T (Treg) cells, a subpopulation of CD4+ T cells with immunosuppressive and anti‐inflammatory properties, are activated in the late stages of the disease. To date, the potential therapeutic usefulness of Treg cells has not been tested. In this study, we aimed to investigate whether Treg cells exert protection/repair following stroke. Both the adoptive transfer of Treg cells into ischaemic rats and the stimulation of endogenous T‐cell proliferation using a CD28 superagonist reduced the infarct size at 3–28 days following the ischaemic insult. Moreover, T cell‐treated animals had higher levels of FoxP3 and lower levels of IL‐1β, CD11b+ and CD68+ cells in the infarcted hemisphere when compared with control animals. However, T‐cell treatment did not alter the rate of proliferation of NeuN‐, NCAM‐ or CD31‐positive cells, thereby ruling out neurogenesis and angiogenesis in protection. These results suggest that adoptive transfer of T cells is a promising therapeutic strategy against the neurological consequences of stroke.