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Adoptive transfer of immune subsets prior to MCAO does not exacerbate stroke outcome in splenectomized mice.

Wang J, Dotson AL, Murphy SJ, Offner H, Saugstad JA - J Syst Integr Neurosci (2015)

Bottom Line: The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO.However, there were significant alterations to the resident peripheral immune composition.These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA.

ABSTRACT

The peripheral immune response contributes to neurologic impairment after stroke and the extent of initial damage is greater in males than females. We have previously shown that spleen cells directly contribute to ischemic damage in males, as splenectomy prior to experimental stroke eliminates the sex differences in infarct volume. This study aims to determine which specific subset of immune cells exert pathogenic effects when injected 24 hours before MCAO induction into splenectomized male and female WT mice. The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO. However, there were significant alterations to the resident peripheral immune composition. These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

No MeSH data available.


Related in: MedlinePlus

Effect of adoptive transfer of CD4/CD8 T cells on blood frequencies of CD4+, CD8+, and CD44+ in splenectomized male and female WT miceBlood was harvested 96 hours after MCAO from splenectomized mice and immunopheno-typed by flow cytometry. The frequencies of CD4+ and CD8+ T cells were determined (A, B). CD4:CD8 ratio was determined by dividing the frequency of CD4+ cells by the frequency of CD8+ cells (C). The frequency of cells expressing CD44 was also examined (D). Values represent mean numbers (± SEM) of the following groups: male saline n=6, male CD4 n=4, male CD8 n=4, female saline n=7, female CD4 n=8, female CD8 n=5. * indicates p<0.05 by t-test.
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Figure 6: Effect of adoptive transfer of CD4/CD8 T cells on blood frequencies of CD4+, CD8+, and CD44+ in splenectomized male and female WT miceBlood was harvested 96 hours after MCAO from splenectomized mice and immunopheno-typed by flow cytometry. The frequencies of CD4+ and CD8+ T cells were determined (A, B). CD4:CD8 ratio was determined by dividing the frequency of CD4+ cells by the frequency of CD8+ cells (C). The frequency of cells expressing CD44 was also examined (D). Values represent mean numbers (± SEM) of the following groups: male saline n=6, male CD4 n=4, male CD8 n=4, female saline n=7, female CD4 n=8, female CD8 n=5. * indicates p<0.05 by t-test.

Mentions: Given that adoptive transfer of CD4+ or CD8+ T cells to splenectomized male or female mice did not exacerbate infarct volume induced by focal ischemia (Figure 1), we examined the effect of MCAO on resident, non-GFP T cell subset frequencies in blood following adoptive transfer of unactivated CD4+ and CD8+ into male and female mice. Figure 6A shows that CD4+ transfer increases CD4+ T cells in the blood after MCAO, while CD8+ transfer decreases CD4+ T cells in the blood after MCAO. In contrast, Figure 6B shows that CD8+ T cells in the blood were largely unaffected after MCAO by transfer of either CD4+ or CD8+. Figure 6C shows that females exhibit an increased baseline CD4:CD8 ratio in the blood after MCAO (supported by Dotson, Wang et. al.), which was not significantly altered by CD8+ transfers and resulted in a loss of sex difference in CD4+ transfers. Figure 6D shows that transfer of CD8+ cells prior to MCAO increases the frequency of CD44+ (activated) cells in the blood.


Adoptive transfer of immune subsets prior to MCAO does not exacerbate stroke outcome in splenectomized mice.

Wang J, Dotson AL, Murphy SJ, Offner H, Saugstad JA - J Syst Integr Neurosci (2015)

Effect of adoptive transfer of CD4/CD8 T cells on blood frequencies of CD4+, CD8+, and CD44+ in splenectomized male and female WT miceBlood was harvested 96 hours after MCAO from splenectomized mice and immunopheno-typed by flow cytometry. The frequencies of CD4+ and CD8+ T cells were determined (A, B). CD4:CD8 ratio was determined by dividing the frequency of CD4+ cells by the frequency of CD8+ cells (C). The frequency of cells expressing CD44 was also examined (D). Values represent mean numbers (± SEM) of the following groups: male saline n=6, male CD4 n=4, male CD8 n=4, female saline n=7, female CD4 n=8, female CD8 n=5. * indicates p<0.05 by t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 6: Effect of adoptive transfer of CD4/CD8 T cells on blood frequencies of CD4+, CD8+, and CD44+ in splenectomized male and female WT miceBlood was harvested 96 hours after MCAO from splenectomized mice and immunopheno-typed by flow cytometry. The frequencies of CD4+ and CD8+ T cells were determined (A, B). CD4:CD8 ratio was determined by dividing the frequency of CD4+ cells by the frequency of CD8+ cells (C). The frequency of cells expressing CD44 was also examined (D). Values represent mean numbers (± SEM) of the following groups: male saline n=6, male CD4 n=4, male CD8 n=4, female saline n=7, female CD4 n=8, female CD8 n=5. * indicates p<0.05 by t-test.
Mentions: Given that adoptive transfer of CD4+ or CD8+ T cells to splenectomized male or female mice did not exacerbate infarct volume induced by focal ischemia (Figure 1), we examined the effect of MCAO on resident, non-GFP T cell subset frequencies in blood following adoptive transfer of unactivated CD4+ and CD8+ into male and female mice. Figure 6A shows that CD4+ transfer increases CD4+ T cells in the blood after MCAO, while CD8+ transfer decreases CD4+ T cells in the blood after MCAO. In contrast, Figure 6B shows that CD8+ T cells in the blood were largely unaffected after MCAO by transfer of either CD4+ or CD8+. Figure 6C shows that females exhibit an increased baseline CD4:CD8 ratio in the blood after MCAO (supported by Dotson, Wang et. al.), which was not significantly altered by CD8+ transfers and resulted in a loss of sex difference in CD4+ transfers. Figure 6D shows that transfer of CD8+ cells prior to MCAO increases the frequency of CD44+ (activated) cells in the blood.

Bottom Line: The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO.However, there were significant alterations to the resident peripheral immune composition.These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA.

ABSTRACT

The peripheral immune response contributes to neurologic impairment after stroke and the extent of initial damage is greater in males than females. We have previously shown that spleen cells directly contribute to ischemic damage in males, as splenectomy prior to experimental stroke eliminates the sex differences in infarct volume. This study aims to determine which specific subset of immune cells exert pathogenic effects when injected 24 hours before MCAO induction into splenectomized male and female WT mice. The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO. However, there were significant alterations to the resident peripheral immune composition. These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

No MeSH data available.


Related in: MedlinePlus