IL-2/IL-2Ab complexes expand regulatory T cells in vivo and provide neuroprotection after cardiac arrest

Immunol Lett. 2026 Apr:278:107113. doi: 10.1016/j.imlet.2025.107113. Epub 2025 Nov 24.

Abstract

Cardiac arrest (CA) results in global ischemia/reperfusion injury and severe neurological dysfunction, for which effective therapeutic interventions remain limited. Regulatory T cells (Tregs) play a crucial role in modulating post-ischemic inflammation and promoting neuroprotection. In this study, we demonstrate that in vivo expansion of Tregs using the interleukin-2/interleukin-2 antibody (IL-2/IL-2Ab) complex significantly increased Treg numbers in the blood, spleen, and lymph nodes. Mice pretreated with the IL-2/IL-2Ab complex before cardiac arrest and cardiopulmonary resuscitation (CA/CPR) exhibited improved neurological recovery, reduced ischemic brain injury, and enhanced survival rates. These findings highlight a potential immunomodulatory strategy for improving outcomes after cardiac arrest. The IL-2/IL-2Ab complex may represent a promising adjunctive therapy to attenuate post-resuscitation brain injury through the selective expansion of protective Tregs.

Keywords: Cardiopulmonary resuscitation; IL-2/IL-2 antibody complex; Neuroprotection; Regulatory T cells.

MeSH terms

  • Animals
  • Cardiopulmonary Resuscitation
  • Disease Models, Animal
  • Heart Arrest* / immunology
  • Heart Arrest* / therapy
  • Interleukin-2* / immunology
  • Interleukin-2* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotection*
  • T-Lymphocytes, Regulatory* / drug effects
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / metabolism

Substances

  • Interleukin-2