EFFECTS OF BRUCELLA ABORTUS AND LPS-BA ON LYMPHOKINE SECRETION

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We are interested in BA as a carrier in the development of human vaccines because it behaves as a T-independent type 1 antigen in stimulating human B cells. That is, it is capable of inducing human B cell responses (i) in the relative absence of T cells, (ii) in neonatal human B cells and (iii) in B cells obtained from patients with the Wiskott-Aldrich syndrome (X-linked immunodeficiency). These properties suggest that BA may be particularly well suited as a carrier for HIV-1 derived proteins or peptides in eliciting responses from HIV-1 infected individuals (with compromised CD4+ T cell function) and in neonates who have HIV-1 infected mothers. Recent evidence suggests that BA is partially dependent on T cell factors, in particular IFNg. In mice this ability to induce IFNg is probably related to the observation that BA elicits a certain IgG subclass pattern characterized by high titer IgG2a. This may be important in the context of viral infections because IgG2a has high affinity for complement and Fc receptors. The main purpose of this project was to investigate the effect of BA on human T cells, especially with respect to IFNg release. It was of interest to determine whether BA could trigger the CD8+ T cell subset because these cells are retained in HIV-1 infected individuals. Stimulation of these latter cells may induce lymphokines and thus bypass the requirement for CD4+ and CD8+ human T cells were capable of responding to BA and secreting IFNg. The IFNg release by human T cells to BA could be synergistically increased in the presence of IL2. This synergism was probably due to the fact that BA could increase the expression of IL-2 receptor on the surface of human T cells. which we demonstrated by flow cytometry.