CD4+ T cells promote delayed B cell responses in the ischemic brain after experimental stroke

Brain Behav Immun. 2021 Jan:91:601-614. doi: 10.1016/j.bbi.2020.09.029. Epub 2020 Sep 28.


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.

Keywords: B-lymphocytes; CD4-positive T-lymphocytes; Chronic inflammation; Cognitive impairment; Stroke; Tertiary lymphoid tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes
  • Brain
  • Brain Ischemia*
  • CD4-Positive T-Lymphocytes
  • Female
  • Infarction, Middle Cerebral Artery
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Stroke*
  • T-Lymphocytes