CD3+ T cell depletion paradoxically worsens intracerebral hemorrhage through blood-brain barrier disruption.

Aim: This study aims to assess the involvement of CD3+ T cells in the early stage of cerebral hemorrhage and investigate how depleting CD3+ T cells affects brain injury.

Methods: We proposed that CD3+ T cell infiltration aggravates hemorrhagic brain injury and observed the changes in brain injury by consuming these cells through the administration of anti-CD3 antibodies. Mice received an intraperitoneal injection of 50 μg of purified anti-CD3 monoclonal antibody 24 hours prior to the induction of intracerebral hemorrhage (ICH), with IgG antibody serving as the control. Results: Compared to the sham group, the ICH+IgG group showed a significant infiltration of CD3+ T cells and CD4+ T cells into the brain. This group also displayed elevated mNSS scores, a reduction in Nissl bodies, brain tissue disorganization, increased AQP4 protein expression, worsened brain edema, impaired BBB integrity, heightened inflammation, and decreased cerebral perfusion. Unexpectedly, depleting CD3+ T cells led to a reduction of these cells in both the circulation and brain, with CD4+ T cells being decreased, whereas CD8+ T cells showed an increase.

Conclusion: CD3+ T cell infiltration can aggravate brain injury related to cerebral hemorrhage, while extensive consumption of CD3+ T cells disrupts immune homeostasis and further exacerbates the injury. Precise regulation of T cell subsets rather than total depletion may be a key strategy for ICH immunotherapy.