Stimulation of both humoral and cellular immune responses to HIV-1 gp120 by interleukin-12 in Rhesus macaques.

The adjuvant effect of recombinant Rhesus macaque interleukin-12 (RhIL-12) on the induction of cellular and humoral immune responses elicited by the HIV-1 subunit vaccine protein gp120 in Rhesus macaques was examined. RhIL-12 in conjunction with gp120 was given at day 0, 28 and 84 intramuscularly. Coadministration resulted in an approximate 10-fold increase in plasma anti-gp120 antibody levels as compared to levels generated in control monkeys receiving gp120 alone.

Discontinuation of treatment with IFN-beta leads to exacerbation of experimental autoimmune encephalomyelitis in Lewis rats. Rapid reversal of the antiproliferative activity of IFN-beta and excessive expansion of autoreactive T cells as disease promoting mechanisms.

IFN-beta has recently been shown to exert remarkable beneficial effects on disease development in patients with early stage relapsing-remitting MS. The specific immune mechanism(s) by which IFN-beta ameliorates this human demyelinating disease is at present undefined. One potential mechanism may reside in the antiproliferative activity of IFN-beta which may inhibit the expansion of autoaggressive T cells thereby limiting disease progression.

The length of treatment determines whether IFN-beta prevents or aggravates experimental autoimmune encephalomyelitis in Lewis rats.

The mechanism of action underlying the beneficial effect of IFN-beta in multiple sclerosis (MS) is not understood. To date, little information is available on the effects of IFN-beta in experimental autoimmune encephalomyelitis (EAE), the animal correlate of the human disease MS. Therefore, we investigated the effects of recombinant rat IFN-beta (rrIFN-beta) on EAE in Lewis rats with emphasis on a treatment regimen during the paralytic phase of the disease.

Enumeration of lymphokine-secreting cells as a quantitative measure for cellular immune responses in rhesus macaques.

We investigated whether enumeration of lymphokine-secreting T cells can be used as a quantitative measure to determine the immunogenicity of foreign proteins in rhesus monkeys. In addition, it was assessed whether this approach can supplement and/or substitute for the well-established lymphoproliferation assay. Two candidate vaccine proteins (e.

Susceptibility to mercuric chloride-induced glomerulonephritis is age-dependent: study of the role of IFN-gamma.

The repeated administration of low-dose HgCl2 to brown Norway (BN) rats induces an autoimmune syndrome which is characterized by polyclonal B cell activation, high-level synthesis of IgE and IgG1, and massive proteinuria. Data have been presented suggesting that during disease development there is a preferential expansion of CD4+ T cells belonging to the TH2 subset. In the present study it was found that aged BN rats are far less susceptible to the immunopathological effects of HgCl2 compared to their younger counterparts.

Nitric oxide suppresses IFN-gamma production in the spleen of mercuric chloride-exposed brown Norway rats.

Recently we have shown that the generation of IFN-gamma-producing cells (IFN-gamma pc) were severely suppressed in cultures of Con A-stimulated splenocytes obtained from HgCl2-exposed BN but not Lewis rats. Since BN rats develop a TH2-biased polyclonal autoimmune syndrome upon exposure to HgCl2, whereas Lewis rats exhibit a resistant phenotype, possibly by generating a protective TH1 response, downregulation of IFN-gamma production may be a critical denominator in the disease process. In the present study it was found that this suppression of IFN-gamma production was almost completely antagonized by NG-monomethyl-L-arginine (NMMA), a competitive inhibitor of nitric oxide (NO) synthesis, and potentiated by the depletion of splenic erythrocytes, a cell type known to effectively scavenge NO.

Mercuric chloride down-regulates T cell interferon-gamma production in brown Norway but not in Lewis rats; role of glutathione.

Injection of a low dose of mercuric chloride into Brown Norway (BN) rats caused a marked decrease in the concanavalin A (ConA)-induced generation of interferon-gamma-producing cells (IFN-gamma pc) in spleen cell cultures prepared 1 h after mercury administration. A second injection 48 h later caused a further diminution of IFN-gamma pc down to 30% of the number generated in splenocyte cultures of phosphate-buffered saline (PBS)-injected controls. Injection of Lewis rats with either one or two doses of HgCl2 revealed no inhibitory effect on splenic IFN-gamma production.

Assessment of the inhibitory effect of immunosuppressive agents on rat T cell interferon-gamma production using an ELISPOT assay.

The immunospot (ELISPOT) assay has proven to be an efficient and sensitive method for the enumeration of single cells secreting antibodies or cytokines. Here we show that the generation of interferon-gamma producing cells (IFN-gamma pc) in rat spleen cell cultures stimulated with concanavalin A (ConA) is dose-dependently inhibited by a wide variety of immunosuppressants such as cyclosporin A, FK506, hydrocortisone, dexamethasone, azathioprine and ART-18, a monoclonal antibody (mAb) with established immunosuppressive activity in organ transplantation and autoimmunity. The minimal inhibitory concentration (m.

Complement-mediated inactivation of interferon-gamma in ELISA systems.

The recovery of a predetermined amount of interferon-gamma (IFN-gamma) added to normal serum was studied in two independent sandwich ELISA systems specific for rat and human IFN-gamma. In both assays the ELISA activity was rapidly lost in fresh but not in heat-inactivated (30', 56 degrees C) serum. Ninety percent of the initial activity had disappeared within 30 minutes upon incubation at 37 degrees C.

A sensitive two-site enzyme immunoassay for the detection of rat interferon-gamma in biological fluids.

Two noncompeting monoclonal antibodies (mAbs) directed to rat interferon-gamma (IFN-gamma) were used in a sensitive two-site enzyme-linked immunosorbent assay (ELISA). This permitted quantitation of rat IFN-gamma in culture medium, and serum and was quicker and more sensitive than the conventional antiviral bioassay. A standard curve was linear between 0.