The peripheral immune response contributes to neurodegeneration after stroke yet little is known about how this process differs between males and females. The current study demonstrates that splenectomy prior to experimental stroke eliminates sex differences in infarct volume and activated brain monocytes/microglia. In the periphery of both sexes, activated T cells correlate directly with stroke outcome while monocytes are reduced by splenectomy only in males. This study provides new information about the sex specific mechanisms of the peripheral immune response in neurodegeneration after stroke and demonstrates the need for representation of both sexes in basic and clinical stroke research.

BackgroundOmalizumab, is a humanized anti-IgE monoclonal antibody used to treat allergic asthma. Decreased serum IgE levels, lower eosinophil and B cell counts have been noted as a result of treatment. In vitro studies and animal models support the hypothesis that omalizumab inhibits IgE synthesis by B cells and causes elimination of IgE-expressing cells either by induction of apoptosis or induction of anergy or tolerance.MethodsWe examined the influence of omalizumab on human tonsillar B cell survival and on the genes involved in IgE synthesis. Tonsillar B cells were stimulated with IL-4 plus anti-CD40 antibody to induce class switch recombination to IgE production in the presence or absence of omalizumab. Cell viability was assessed and RNA extracted to examine specific genes involved in IgE synthesis.ConclusionsWe found that omalizumab reduced viable cell numbers but this was not through induction of apoptosis. IL-4R and germline Cϵ mRNA levels were decreased as well as the number of membrane IgE+ cells in B cells treated with omalizumab. These data suggest that omalizumab may decrease IgE synthesis by human B cells by specifically targeting membrane IgE-bearing B cells and inducing a state of anergy.

The iron chelator, Desferal, suppressed disease activity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and it has been tested in pilot trials for MS. The administration regimen of Desferal is cumbersome and prone to complications. Orally-deliverable, iron chelators have been developed that circumvent these difficulties, and the objective of this study was to test an oral chelator in EAE. SJL mice with active EAE were randomly assigned to receive deferiprone (150 mg/kg) or vehicle (water) 2x/day via gavage. EAE mice given deferiprone had significantly less disease activity and lower levels of inflammatory cell infiltrates (revealed by H&E staining) than EAE mice administered vehicle. T-cell infiltration, assessed by anti-CD3 immunohistochemical staining, also was reduced, although not significantly. Splenocytes cultured from naïve SJL mice were stimulated with anti-CD3 and anti-CD28 with or without 250 microM deferiprone. While approximately 39% of costimulated splenocytes without deferiprone underwent division, only approximately 2.8% of costimulated splenocytes with deferiprone divided and the latter cells were only 53% as viable as the former. Deferiprone had no effect on proliferation or viability of cells that were not costimulated. In summary, deferiprone effectively suppressed active EAE disease and it inhibited T-cell function.

Type 1 diabetes (T1D) is characterized by hyperglycemia due to lost or damaged islet insulin-producing β-cells. Rodent models of T1D result in hyperglycemia, but with different forms of islet deterioration. This study focused on 1 toxin-induced and 2 autoimmune rodent models of T1D: BioBreeding Diabetes Resistant rats, nonobese diabetic mice, and Dark Agouti rats treated with streptozotocin. Immunochemistry was used to evaluate the insulin levels in the β-cells, cell composition, and insulitis. T1D caused complete or significant loss of β-cells in all animal models, while increasing numbers of α-cells. Lymphocytic infiltration was noted in and around islets early in the progression of autoimmune diabetes. The loss of lymphocytic infiltration coincided with the absence of β-cells. In all models, the remaining α- and δ-cells regrouped by relocating to the islet center. The resulting islets were smaller in size and irregularly shaped. Insulin injections subsequent to induction of toxin-induced diabetes significantly preserved β-cells and islet morphology. Diabetes in animal models is anatomically heterogeneous and involves important changes in numbers and location of the remaining α- and δ-cells. Comparisons with human pancreatic sections from healthy and diabetic donors showed similar morphological changes to the diabetic BBDR rat model.