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

Authors

  • David Brea,

    1. Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
    2. Cellular and Molecular Neurobiology Research Group and Grup de Recerca en Neurociencies del IGTP, Department of Neurosciences, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias I Pujol-Universitat Autónoma de Barcelona, Badalona, Spain
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  • Jesús Agulla,

    1. Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
    2. Instituto de Investigación Biomédica de Salamanca, Hospital Universitario de Salamanca, Salamanca, Spain
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  • Manuel Rodríguez-Yáñez,

    1. Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
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  • David Barral,

    1. Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
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  • Pedro Ramos-Cabrer,

    1. Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
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  • Francisco Campos,

    1. Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
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  • Angeles Almeida,

    1. Instituto de Investigación Biomédica de Salamanca, Hospital Universitario de Salamanca, Salamanca, Spain
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  • Antoni Dávalos,

    1. Cellular and Molecular Neurobiology Research Group and Grup de Recerca en Neurociencies del IGTP, Department of Neurosciences, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias I Pujol-Universitat Autónoma de Barcelona, Badalona, Spain
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  • José Castillo

    Corresponding author
    1. Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
    • Correspondence to: Prof. José CASTILLO, Servicio de Neurología, Hospital Clínico Universitario, Travesa da Choupana s/n, 15706 Santiago de Compostela, Spain.

      Tel.: +34981951086

      Fax: +34981951098

      E-mail: jose.castillo.sanchez@sergas.es

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Abstract

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.

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