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Isolation and Flow Cytometric Analysis of Immune Cells from the Ischemic Mouse Brain
Published on: February 12, 2016
CD4+ T cells promote delayed B cell responses in the ischemic brain after experimental stroke
Luis Weitbrecht1, Daniel Berchtold1, Tian Zhang1
1Charité - Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Experimental Neurology, Germany.
Insights
CD4+ T cells drive delayed B cell infiltration into the ischemic brain after stroke. Depleting these cells improved cognitive function, suggesting new therapies for post-stroke cognitive impairment.
Area of Science:
- Neuroimmunology
- Stroke Pathophysiology
- Immune Cell Dynamics
Background:
- CD4+ T lymphocytes are implicated in ischemic stroke tissue damage.
- The role of CD4+ T cells in delayed immune responses and B cell interactions post-stroke is not well understood.
- Post-stroke cognitive impairment (PSCI) is linked to autoreactive B cell responses.
Purpose of the Study:
- To investigate the role of CD4+ T cells in delayed B cell infiltration into the ischemic brain.
- To determine the impact of CD4+ T cell depletion on lymphocyte kinetics and cognitive outcomes after stroke.
- To explore potential therapeutic strategies for PSCI by modulating CD4+ T cell activity.
Main Methods:
- Utilized myelin oligodendrocyte glycoprotein T cell receptor transgenic 2D2 mice treated with anti-CD4 antibody after middle cerebral artery occlusion.
- Monitored lymphocyte infiltration, including CD4+ T cells and B cells, in the brain for up to 72 days.
- Assessed infarct maturation, survival rates, and cognitive functions.
Main Results:
- Anti-CD4 treatment effectively depleted CD4+ T cells from circulation and the ischemic brain for 28 days.
- B cell infiltration into the brain was significantly inhibited by CD4+ T cell depletion, especially in large infarcts.
- Following CD4+ T cell recovery, both CD4+ T and B cells infiltrated the infarct site, forming follicle-like structures.
- CD4 depletion attenuated cognitive deficits in experimental models of PSCI.
Conclusions:
- CD4+ T cells are crucial for the delayed infiltration of B cells into the ischemic brain post-stroke.
- Lymphocyte infiltration into the brain is a prolonged process following ischemic events.
- Targeting CD4+ T cell-mediated immune responses holds promise for developing novel therapeutic interventions for PSCI.
Abstract:
CD4+ T lymphocytes are key mediators of tissue damage after ischemic stroke. However, their infiltration kinetics and interactions with other immune cells in the delayed phase of ischemia remain elusive. We hypothesized that CD4+ T cells facilitate delayed autoreactive B cell responses in the brain, which have been previously linked to post-stroke cognitive impairment (PSCI). Therefore, we treated myelin oligodendrocyte glycoprotein T cell receptor transgenic 2D2 mice of both sexes with anti-CD4 antibody following 60-minute middle cerebral artery occlusion and assessed lymphocyte infiltration for up to 72 days. Anti-CD4-treatment eliminated CD4+ T cells from the circulation and ischemic brain for 28 days and inhibited B cell infiltration into the brain, particularly in animals with large infarcts. Absence of CD4+ T cells did not influence infarct maturation or survival. Once the CD4+ population recovered in the periphery, both CD4+ T and B lymphocytes entered the infarct site forming follicle-like structures. Additionally, we provide further evidence for PSCI that could be attenuated by CD4 depletion. Our findings demonstrate that CD4+ T cells are essential in delayed B cell infiltration into the ischemic brain after stroke. Importantly, lymphocyte infiltration after stroke is a long-lasting process. As CD4 depletion improved cognitive functions in an experimental set-up, these findings set the stage to elaborate more specific immune modulating therapies in treating PSCI.
