Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages

Halina Offner, Sandhya Subramanian, Susan M. Parker, Chunhe Wang, Michael E. Afentoulis, Anne Lewis, Arthur Vandenbark, Patricia D. Hurn

Research output: Contribution to journalArticle

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Abstract

Induction of stroke not only produces local ischemia and brain damage, but also has profound effects on peripheral immune responses. In the current study, we evaluated effects on spleen and blood cells 4 days after stroke induction. Surprisingly, there was a less inflammatory cytokine profile in the middle cerebral artery occlusion-affected right brain hemisphere at 96 h compared with earlier time points. Moreover, our results demonstrate that stroke leads to splenic atrophy characterized by a reduction in organ size, a drastic loss of splenocyte numbers, and induction of annexin V+ and TUNEL+ cells within the spleen that are in the late stages of apoptosis. The consequence of this process was to reduce T cell proliferation responses and secretion of inflammatory cytokines, resulting in a state of profound immunosuppression. These changes produced a drastic reduction in B cell numbers in spleen and blood, and a novel increase in CD4+FoxP3+ regulatory T cells. Moreover, we detected a striking increase in the percentage of nonapoptotic CD11b+ VLA-4-negative macrophages/monocytes in blood. Immunosuppression in response to brain injury may account for the reduction of inflammatory factors in the stroke-affected brain, but also potentially could curtail protective immune responses in the periphery. These findings provide new evidence to support the contention that damage to the brain caused by cerebral ischemia provides a powerful negative signal to the peripheral immune system that ultimately induces a drastic state of immunosuppression caused by cell death as well as an increased presence of CD4+FoxP3+ regulatory T cells.

Original languageEnglish (US)
Pages (from-to)6523-6531
Number of pages9
JournalJournal of Immunology
Volume176
Issue number11
StatePublished - Jun 1 2006

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Regulatory T-Lymphocytes
Atrophy
Stroke
Macrophages
Immunosuppression
Spleen
Brain Ischemia
Brain
Cytokines
Integrin alpha4beta1
Organ Size
Annexin A5
Middle Cerebral Artery Infarction
In Situ Nick-End Labeling
Brain Injuries
Monocytes
Immune System
Blood Cells
B-Lymphocytes
Cell Death

ASJC Scopus subject areas

  • Immunology

Cite this

Offner, H., Subramanian, S., Parker, S. M., Wang, C., Afentoulis, M. E., Lewis, A., ... Hurn, P. D. (2006). Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. Journal of Immunology, 176(11), 6523-6531.

Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. / Offner, Halina; Subramanian, Sandhya; Parker, Susan M.; Wang, Chunhe; Afentoulis, Michael E.; Lewis, Anne; Vandenbark, Arthur; Hurn, Patricia D.

In: Journal of Immunology, Vol. 176, No. 11, 01.06.2006, p. 6523-6531.

Research output: Contribution to journalArticle

Offner, Halina ; Subramanian, Sandhya ; Parker, Susan M. ; Wang, Chunhe ; Afentoulis, Michael E. ; Lewis, Anne ; Vandenbark, Arthur ; Hurn, Patricia D. / Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. In: Journal of Immunology. 2006 ; Vol. 176, No. 11. pp. 6523-6531.
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