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(Stroke. 2003;34:1809.)
© 2003 American Heart Association, Inc.

Original Contributions

Adoptive Transfer of Myelin Basic Protein–Tolerized Splenocytes to Naive Animals Reduces Infarct Size

A Role for Lymphocytes in Ischemic Brain Injury?

Kyra Becker, MD; Darin Kindrick, BS; Richard McCarron, PhD; John Hallenbeck, MD Robert Winn, PhD

From the Departments of Neurology (K.B., D.K.) and Surgery (R.W.), University of Washington School of Medicine, Harborview Medical Center, Seattle, Wash; Resuscitative Medicine Department, Naval Medical Research Center, Silver Spring, Md (R.M.); and Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md (J.H.).

Reprint requests to Kyra J. Becker, MD, Box 359775, Harborview Medical Center, 325 Ninth Ave, Seattle, WA 98104-2499. E-mail kjb{at}u.washington.edu

Background and Purpose— Breakdown of the blood-brain barrier during stroke allows central nervous system antigens to leak into the systemic circulation and allows circulating leukocytes access to the brain. Encounter of central nervous system antigens by the peripheral immune system can be capitalized on to modulate the postischemic inflammatory response and potentially improve outcome from stroke.

Methods— Male Lewis rats were tolerized to myelin basic protein (MBP) or ovalbumin (OVA) and subjected to 3 hours of middle cerebral artery occlusion (MCAO) or used as splenocyte donors for immunologically naive animals undergoing MCAO. Infarct size was determined at 24 hours by 2,3,5-triphenyltetrazolium chloride staining. In separate studies, mononuclear cells were removed from the brains of animals after MCAO for enzyme-linked immunospot (ELISPOT) assay and flow cytometry.

Results— Median infarct volume in animals tolerized to MBP and those receiving splenocytes from MBP-tolerized donors was less than in animals tolerized to OVA and those receiving splenocytes from OVA-tolerized donors (87.7±54.9 versus 148±61.6 mm³ [P=0.01] and 89.2±77.5 versus 153±77.1 mm³ [P=0.05], respectively). There was an increase in the number of transforming growth factor-ß1–secreting mononuclear cells in MBP-tolerized animals undergoing sham surgery (P=0.001) as well as in ischemic animals 48 hours (P=0.02) and 336 hours (P=0.04) after stroke. A distinct subset of T cells was present in the brains of MBP-tolerized but not control animals after stroke.

Conclusions— Immunologic tolerance and its neuroprotective effects can be transferred to naive animals and appear to be related to antigen-specific induction of transforming growth factor-ß1.

Key Words: cytokines • immune tolerance • inflammation • stroke • T-lymphocytes

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