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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+ and CD8+ on frequency of CD11b+, CD11c+ and CD19+ cells in blood after MCAO in splenectomized male and female WT miceMCAO from splenectomized mice and immunophenotyped by flow cytometry. The frequencies of CD11b+, CD11c+ and CD19+ cells were determined (A,B,C). 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 7: Effect of adoptive transfer of CD4+ and CD8+ on frequency of CD11b+, CD11c+ and CD19+ cells in blood after MCAO in splenectomized male and female WT miceMCAO from splenectomized mice and immunophenotyped by flow cytometry. The frequencies of CD11b+, CD11c+ and CD19+ cells were determined (A,B,C). 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: We further examined the effect of MCAO on CD11b+, CD11c+ and CD19+ cells in blood following adoptive transfer of unactivated CD4+ and CD8+ into male and female mice. Figure 7A shows that transfer of CD8+ cells prior to MCAO increases the frequency CD11b+ monocytes/ macrophages in the blood. In contrast, Figure 7B shows that transfer of either cell type does not significantly affect the frequency of positive CD11c+ dendritic cells in blood. However, Figure 7C shows that transfer of CD8+ cells prior to MCAO decreased the frequency of potentially protective CD19+ B cells in the blood in males, but this effect is less pronounced in females. These studies support that transfer of CD8+ T cells prior to MCAO leads to more potentially harmful immune cell subsets 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+ and CD8+ on frequency of CD11b+, CD11c+ and CD19+ cells in blood after MCAO in splenectomized male and female WT miceMCAO from splenectomized mice and immunophenotyped by flow cytometry. The frequencies of CD11b+, CD11c+ and CD19+ cells were determined (A,B,C). 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

License
Show All Figures
getmorefigures.php?uid=PMC4664464&req=5

Figure 7: Effect of adoptive transfer of CD4+ and CD8+ on frequency of CD11b+, CD11c+ and CD19+ cells in blood after MCAO in splenectomized male and female WT miceMCAO from splenectomized mice and immunophenotyped by flow cytometry. The frequencies of CD11b+, CD11c+ and CD19+ cells were determined (A,B,C). 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: We further examined the effect of MCAO on CD11b+, CD11c+ and CD19+ cells in blood following adoptive transfer of unactivated CD4+ and CD8+ into male and female mice. Figure 7A shows that transfer of CD8+ cells prior to MCAO increases the frequency CD11b+ monocytes/ macrophages in the blood. In contrast, Figure 7B shows that transfer of either cell type does not significantly affect the frequency of positive CD11c+ dendritic cells in blood. However, Figure 7C shows that transfer of CD8+ cells prior to MCAO decreased the frequency of potentially protective CD19+ B cells in the blood in males, but this effect is less pronounced in females. These studies support that transfer of CD8+ T cells prior to MCAO leads to more potentially harmful immune cell subsets 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