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The effects of 17β-estradiol (E2) on immune function have been extensively reported. The effects are dependent on concentration and duration of exposure and potential differences in signaling between the known E2 receptors, estrogen receptors (ER) α and ERβ. Through the use of ER-deficient mice, we and others have begun to demonstrate the role of the two known receptors in modulating immune functional activities. Previous studies have shown that cells of the innate immune system have altered function (bactericidal capacity) and patterns of cytokine expression (increased proinflammatory cytokine expression) through amelioration of ERα signaling. In this study, we extend these studies to analysis of T cell differentiation and proliferation in APC-dependent and APC-independent in vitro assay systems. Our results demonstrate that ERα deficiency in splenic macrophages, but not CD11c+ splenic dendritic cells pulsed with OVA significantly enhances proliferative responses and IFN-γ production by transgenic OVA peptide-specific (OT-II) CD4+ T cells when compared with Ag-pulsed APC from wild-type littermates. The addition of E2 in this culture system did not significantly affect the production of IFN-γ. In addition, when purified CD4+ T cells from ERα-deficient and wild-type littermates were stimulated with anti-CD3/CD28 Ab in the absence of E2, there were no significant differences in IFN-γ or IL-4 production. However, the addition of E2 significantly increased IL-4 secretion, as well as increased GATA-3 mRNA levels from ERα-replete CD4+ T cells, while this effect was abrogated in ERα-deficient CD4+ T cells.

Burkholderia mallei is a gram-negative highly pathogenic bacterium, responsible for glanders. B. mallei is considered potential bioterrorism agents, classified as such in list B by the Centers for Disease Control and Prevention. Currently there is no vaccine available against B. mallei. In this study, we aimed to identify the protective proteins of B. mallei. The candidate proteins were selected based on the previous data of proteomics and linear expression library (LEE) whole-genome screens coupled with known structures or functions of the proteins in other bacteria. The selected proteins were BMA-4, BMA-8, BMA-9, BMA-10, BMA-11 and BMA-12. The genes encoding each protein were cloned into pCDNA3.1 and pET28a. The His-tag proteins were then purified. BALB/c mice were vaccinated with DNA encoding each protein and then boosted 3 weeks later with the recombinant proteins. Two weeks after boosting, mice were infected with B. mallei ATCC23344. The result showed that, 19 days after infection, there was 100% survival in the BMA2821 and BMAA0768 groups, however only 78% survival in the control group. The study needs to be repeated and the result will be discussed.

Burkholderia mallei, the etiologic agent of glanders disease, is a gram-negative, intracellular bacterium for which no vaccine is available. Consequently, we are interested in defining protective host immune responses to B. mallei infection with the goal of developing candidate vaccines. Here, we report on initial cell/cytokine depletion studies to investigate the possible role these effectors may play in response to vaccination with heat killed bacilli in a susceptible BALB/c mouse model of infection. While protection with heat killed bacilli does not result in sterilizing immunity, protection is afforded against an otherwise lethal infection and provides insight into potential host protective mechanisms. Our results demonstrate that mice treated with either anti-B220, TNF-α or IFN-γ monoclonal antibodies exhibited decreased survival rates, indicating a key role for vaccine induced antibody and early cytokine production in protection from lethal challenge infection by the intraperitoneal route.