Distinctive effects of T cell subsets in neuronal injury induced by cocultured splenocytes in vitro and by in vivo stroke in mice.
OBJECTIVE
T cells and their subsets modulate ischemic brain injury. We studied the effects of the absence of T cell subsets on brain infarction after in vivo stroke and then used an in vitro coculture system of splenocytes and neurons to further identify the roles of T cell subsets in neuronal death.


METHODS
Stroke was induced by middle cerebral artery suture occlusion in mice and infarct sizes were measured 2 days poststroke. Splenocytes were cocultured with neurons, and neuronal survival was measured 3 days later.


RESULTS
A deficiency of both T and B cells (severe combined immunodeficiency) and the paucity of CD4 or CD8 T cells equally resulted in smaller infarct sizes as measured 2 days poststroke. Although a functional deficiency of regulatory T cells had no effect, impaired Th1 immunity reduced infarction and impaired Th2 immunity aggravated brain injury, which may be due to an inhibited and enhanced inflammatory response in mice deficient in Th1 and Th2 immunity, respectively. In the in vitro coculture system, wild-type splenocytes resulted in dose-dependent neuronal death. The neurotoxicity of splenocytes from these immunodeficient mice was consistent with their effects on stroke in vivo, except for the mice with the paucity of CD4 or CD8 T cells, which did not alter the ratio of neuronal death.


CONCLUSIONS
T cell subsets play critical roles in brain injury induced by stroke. The detrimental versus beneficial effects of Th1 cells and Th2 cells both in vivo and in vitro reveal differential therapeutic target strategies for stroke treatment.
Department of Neurosurgery, Stanford University School of Medicine, MSLS Building, P306, 1201 Welch Road, Room P306, Stanford, CA 94305-5327, USA.
Lijuan
L
Gu
Xiaoxing
X
Xiong
Hongfei
H
Zhang
Baohui
B
Xu
Gary K
GK
Steinberg
Heng
H
Zhao
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology*; D013154:Spleen / Q000473:pathology*; D020521:Stroke / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000473:pathology*