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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

Adoptive transfer of activated CD4/CD8 T cells, 24 h before MCAO, does not increase infarct volume in splenectomized male WT miceMice were injected with activated CD4+ or CD8+ T cells 24 hours prior to MCAO. Brains were harvested 96 h after MCAO. (A) Infarct volumes measured as percentage of corrected contralateral structure for male mice injected with saline vehicle (n=4), 12 million CD4+ T cells (n=7), or 8 million CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. (B) Neurological deficit score measured in male mice injected with saline vehicle (n=4), 12 million activated CD4+ T cells (n=7), or 8 million activated CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. (C) Cerebral blood flow measured in male mice injected with saline vehicle (n=4), 12 million activated CD4+ T cells (n=7), or 8 million activated CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. Values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA. Functional outcomes for neurological deficit scores were analyzed by Mann Whitney Rank Sum test. Statistical significance was p<0.05.
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Figure 4: Adoptive transfer of activated CD4/CD8 T cells, 24 h before MCAO, does not increase infarct volume in splenectomized male WT miceMice were injected with activated CD4+ or CD8+ T cells 24 hours prior to MCAO. Brains were harvested 96 h after MCAO. (A) Infarct volumes measured as percentage of corrected contralateral structure for male mice injected with saline vehicle (n=4), 12 million CD4+ T cells (n=7), or 8 million CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. (B) Neurological deficit score measured in male mice injected with saline vehicle (n=4), 12 million activated CD4+ T cells (n=7), or 8 million activated CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. (C) Cerebral blood flow measured in male mice injected with saline vehicle (n=4), 12 million activated CD4+ T cells (n=7), or 8 million activated CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. Values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA. Functional outcomes for neurological deficit scores were analyzed by Mann Whitney Rank Sum test. Statistical significance was p<0.05.

Mentions: Given the lack of effect of CD4 and CD8 adoptive transfer into male and female mice on ischemic injury (Figure 1), we then examined the effect of transferring activated CD4+ and CD8+ T cells on infarct volume in male mice. Donor mice were immunized with MOG, a brain antigen that is known to induce strong pathogenic T cell responses in rodents in vivo. Mice were injected with saline (n = 4), 12 million activated CD4+ T cells (n = 7), or 8 million activated CD8+ T cells (n = 7) 24 h prior to MCAO. Brains were harvested 96 h after MCAO. Figure 4A shows that there is no effect of intravenous transfer of activated CD4+ or CD8+ T cells on infarct volumes, measured as percentage of corrected contralateral structure. Values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA. Figure 4B shows the neurological deficit scores measured in male mice injected with saline vehicle (n = 4), 12 million activated CD4+ T cells (n = 7), or 8 million activated CD8+ T cells (n = 7) by intravenous transfer 24 h before MCAO. Functional outcomes for neurological deficit scores were analyzed by Mann Whitney Rank Sum test. Statistical significance was p<0.05. Figure 4C shows cerebral blood flow measured in male mice injected with saline vehicle (n = 4), 12 million activated CD4+ T cells (n = 7), or 8 million activated CD8+ T cells (n = 7) by intravenous transfer 24 h before MCAO. Values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA.


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)

Adoptive transfer of activated CD4/CD8 T cells, 24 h before MCAO, does not increase infarct volume in splenectomized male WT miceMice were injected with activated CD4+ or CD8+ T cells 24 hours prior to MCAO. Brains were harvested 96 h after MCAO. (A) Infarct volumes measured as percentage of corrected contralateral structure for male mice injected with saline vehicle (n=4), 12 million CD4+ T cells (n=7), or 8 million CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. (B) Neurological deficit score measured in male mice injected with saline vehicle (n=4), 12 million activated CD4+ T cells (n=7), or 8 million activated CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. (C) Cerebral blood flow measured in male mice injected with saline vehicle (n=4), 12 million activated CD4+ T cells (n=7), or 8 million activated CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. Values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA. Functional outcomes for neurological deficit scores were analyzed by Mann Whitney Rank Sum test. Statistical significance was p<0.05.
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Related In: Results  -  Collection

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Figure 4: Adoptive transfer of activated CD4/CD8 T cells, 24 h before MCAO, does not increase infarct volume in splenectomized male WT miceMice were injected with activated CD4+ or CD8+ T cells 24 hours prior to MCAO. Brains were harvested 96 h after MCAO. (A) Infarct volumes measured as percentage of corrected contralateral structure for male mice injected with saline vehicle (n=4), 12 million CD4+ T cells (n=7), or 8 million CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. (B) Neurological deficit score measured in male mice injected with saline vehicle (n=4), 12 million activated CD4+ T cells (n=7), or 8 million activated CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. (C) Cerebral blood flow measured in male mice injected with saline vehicle (n=4), 12 million activated CD4+ T cells (n=7), or 8 million activated CD8+ T cells (n=7) by intravenous transfer 24 h before MCAO. Values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA. Functional outcomes for neurological deficit scores were analyzed by Mann Whitney Rank Sum test. Statistical significance was p<0.05.
Mentions: Given the lack of effect of CD4 and CD8 adoptive transfer into male and female mice on ischemic injury (Figure 1), we then examined the effect of transferring activated CD4+ and CD8+ T cells on infarct volume in male mice. Donor mice were immunized with MOG, a brain antigen that is known to induce strong pathogenic T cell responses in rodents in vivo. Mice were injected with saline (n = 4), 12 million activated CD4+ T cells (n = 7), or 8 million activated CD8+ T cells (n = 7) 24 h prior to MCAO. Brains were harvested 96 h after MCAO. Figure 4A shows that there is no effect of intravenous transfer of activated CD4+ or CD8+ T cells on infarct volumes, measured as percentage of corrected contralateral structure. Values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA. Figure 4B shows the neurological deficit scores measured in male mice injected with saline vehicle (n = 4), 12 million activated CD4+ T cells (n = 7), or 8 million activated CD8+ T cells (n = 7) by intravenous transfer 24 h before MCAO. Functional outcomes for neurological deficit scores were analyzed by Mann Whitney Rank Sum test. Statistical significance was p<0.05. Figure 4C shows cerebral blood flow measured in male mice injected with saline vehicle (n = 4), 12 million activated CD4+ T cells (n = 7), or 8 million activated CD8+ T cells (n = 7) by intravenous transfer 24 h before MCAO. Values represent mean numbers (± SEM) of splenectomized mice per group analyzed using a one-way ANOVA.

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