Exposure to infective larvae of the filarial nematode Onchocerca volvulus (Ov) either results in patent infection (microfilaridermia) or it leads to a status called putative immunity, characterized by resistance to infection. Similar to other chronic helminth infections, there is a T cell proliferative hyporesponsiveness to Ov antigen (OvAg) by peripheral blood mononuclear cells (PBMC) from individuals with patent infection, i.e. generalized onchocerciasis (GEO), compared to PBMC from putatively immune (PI) individuals. In this study, mechanisms mediating this cellular hyporesponsiveness in GEO were investigated: the low proliferative response in PBMC from GEO individuals was associated with a lack of IL-4 production and significantly lower production of IL-5 compared to those from PI individuals, arguing against a general shift towards a T(h)2 response being the cause of hyporesponsiveness. In contrast, IL-10 and transforming growth factor (TGF)-beta, two cytokines associated with a T(h)3 response, seemed to mediate hyporesponsiveness: PBMC from individuals with GEO produced significantly more IL-10, and T cell proliferative hyporesponsiveness in this group could be reversed by the addition of anti-IL-10 and anti-TGF-beta antibodies. Hyporesponsiveness was specific for OvAg and not observed upon stimulation with related nematode antigens, arguing for a T cell-mediated, Ov-specific down-regulation. Ov-specific T cells could be cloned from GEO PBMC which have a unique cytokine profile (no IL-2 but high IL-10 and/or TGF-beta production), similar to the T cell subsets known to suppress ongoing inflammation (T(h)3 and T(r)1), indicating that this cell type which has not been found so far in infectious diseases may be involved in maintaining Ov-specific hyporesponsiveness.
Grampositive bacteria produce a variety of exoproteins, many of which are toxins or otherwise involved in pathogenicity or virulence. The Staphylococcal enterotoxins (SE)' comprise a group of structurally related but serologically distinct proteins produced by certain strains of Straphylococcus aureus (1, 2). Five serological groups (A, B, C, D, and E) of SE have been identified, based on their reactivity with monospecific antisera . SE are the most frequent cause of food poisoning in humans (1, 2) . In addition, SE are the most potent mitogens known, stimulating human or murine lymphocytes at concentrations of <10' M efficiently (3). The only known mitogen active at similarly low concentrations are mAbs against CD3. SE belong to the most widely used mitogens, since SEA and SEB contaminations are the mitogenic principle in Staphylococcal protein A (4). In vivo application of SE leads to polyclonal T cell activation (5) and has significant suppressive effects on cellular and humoral immune responses in vivo (6).The mechanism of T cell activation by SE is unknown. The extremely low concentration of mitogen required for T cell activation suggests a highly selective mechanism in contrast to mitogenic lectins that bind to many structures on T lymphocytes and accessory cells (AC) and require at least 1,000 times higher concentrations .In this report, we have analyzed the molecular mechanism of T cell activation by SE . The experimental data show that reactivity to SE is clonally expressed and that MHC class II molecules are required for T cell triggering by SE. A possible explanation of these findings is that SE are functionally bivalent molecules leading to a selective crosslinking of the T cell receptor/CD3 complex with MHC class II molecules.
Borna disease virus causes a rare meningoencephalitis in horses and sheep and has been shown to produce behavioral effects in some species. The possibility that the Borna virus is associated with mental disorders in humans was evaluated by examining serum samples from 979 psychiatric patients and 200 normal volunteers for the presence of Borna virus-specific antibodies. Antibodies were detected by the indirect immunofluorescence focus assay. Antibodies to the virus were demonstrated in 16 of the patients but none of the normal volunteers. The patients with the positive serum samples were characterized by having histories of affective disorders, particularly of a cyclic nature. Further studies are needed to define the possible involvement of Borna virus in human psychiatric disturbances.
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