HIV-1 Gag p24-Nef fusion peptide induces cellular and humoral immune response in a mouse model.

UNLABELLED: Many Human immunodeficiency virus (HIV) candidate vaccines have been tested in clinical trials, but none was sufficiently effective in the prevention of HIV infection. A HIV vaccine should induce humoral as well as cell-mediated response, the latter including the cytotoxic CD8+ T lymphocyte (CTL) response. In this study, we immunized BALB/c mice with a purified fusion peptide Gag p24-Nef and evaluated immune responses. As for the cellular responses, the adjuvanted fusion peptide induced lymphocyte proliferation, CTL response, and cytokines IFN-gamma and IL-4 in the Th1 pattern. Humoral immune response to the adjuvanted fusion peptide included an increase in IgG antibodies of more IgG2a than IgG1 subtype. These results indicate that the employed HIV-1 peptide construct can elicit both cellular and humoral immune responses in mice. Further studies aimed at memory T cells and other aspects of immune responses are needed before a comprehensive assessment of this candidate vaccine could be provided. KEYWORDS: epitopes; fusion peptide; HIV-1 p24-Nef; immune response.

Immune and nervous systems share molecular and functional similarities: memory storage mechanism.

One of the most complex and important features of both the nervous and immune systems is their data storage and retrieval capability. Both systems encounter a common and complex challenge on how to overcome the cumbersome task of data management. Because each neuron makes many synapses with other neurons, they are capable of receiving data from thousands of synaptic connections. The immune system B and T cells have to deal with a similar level of complexity because of their unlimited task of recognizing foreign antigens. As for the complexity of memory storage, it has been proposed that both systems may share a common set of molecular mechanisms. Here, we review the molecular bases of memory storage in neurons and immune cells based on recent studies and findings. The expression of certain molecules and mechanisms shared between the two systems, including cytokine networks, and cell surface receptors, are reviewed. Intracellular signaling similarities and certain mechanisms such as diversity, memory storage, and their related molecular properties are briefly discussed. Moreover, two similar genetic mechanisms used by both systems is discussed, putting forward the idea that DNA recombination may be an underlying mechanism involved in CNS memory storage.

Neuropeptides (sp and CGRP) augment IL-1 Beta production in hsv-infected macrophages.

Neuropeptides, possessing specific and functional receptors on various cells of the immune system, have the potential to regulate immune responses; and the macrophages as important components of defense against various agents, are at their influence. In this study the effect of neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) on IL-1 beta production by herpes simplex type-1 (HSV-1)-infected and also uninfected mouse peritoneal macrophages were considered. Each neuropeptide separately has upregulated IL-1 beta production by HSV- 1 infected macrophages with the greatest effect at the concentrations of 1 09M for both SP and CGRP, but no synergistic effect on IL-1 production has been observed in the presence of both neuropeptides at optimal concentrations. IL-113 production by uninfected macrophages was also moderately enhanced in the presence of each neuropeptide, but not in the presence of both neuropeptides simultaneously. It can be concluded that IL-1 beta production, which is part of macrophage mediated inflammatory response to HSV-l, is enhanced by specific doses of neuropeptides.

Modeling for immunosuppression by sulfur mustard.

The treatment and cure of patients exposed to sulfur mustard is a remaining challenge despite on-going research in this field. A severe suppression of the immune system still remains the major cause of opportunistic infections, septicemia and death in patients injured by sulfur mustard. In this report, we present a model of sulfur mustard contamination in mice, which exhibit clinical signs similar to that exhibited by patients during the Iran-Iraq war. Dose response studies were performed to determine the most appropriate dose for our model i.e., 6.35 micrograms/kg. Animals contaminated with sulfur mustard intraperitoneally showed symptoms of anorexia, diarrhea, loss of weight and blindness. Autopsy of animals showed a severe necrosis in gut and degeneration of spleen. Results shows that sulfur mustard caused an over all suppression of the immune response to sRBC as indicated by agglutination titer and DTH tests. These studies present a rodent model of sulfur mustard exposure, which can be used for further studies in this area.

Garlic induces a shift in cytokine pattern in Leishmania major-infected BALB/c mice.

The regulation of T helper (Th)1- and Th2-type cytokine patterns is important in the final outcome of leishmaniasis in human and murine models. We examined the efficacy of garlic therapy or a combination of garlic and an antimonial drug (glucantime) in promoting healing and regulation of Th1/Th2 cytokine patterns in highly susceptible BALB/c mice infected with Leishmania major. Separate groups of infected mice received 20 mg/kg/day garlic, 60 mg/kg/day glucantime or a combination of the two, from day 30 after infection for 2 weeks. An enzyme-linked immunosorbant assay (ELISA) was performed on spleen cell culture supernatants for interferon(IFN)-gamma interleukin(IL)-2, IL-4 and IL-10. The results indicate that garlic therapy is more effective than the usual antileishmanial drug in curing the infection. Garlic-treated mice developed Th1-type cytokine responses. In contrast, glucantime therapy led to a Th2-type response in the control group with a lower level of IL-2. However, a combination of garlic and glucantime treatment was more effective than either treatment alone, and resulted in a Th1-type response similar to that which developed with garlic treatment. These results suggest that garlic extract in combination with an antimonial drug, may provide effective therapy against L. major. The immunomodulatory properties of garlic were elucidated in terms of shifting the cytokine response to a Th1-type pattern and therefore causing the protective response.

Differential antigenic stimulation influences cytokine production patterns in T cells and CD4+ subpopulations.

The regulatory mechanisms that govern the commitment of T cells to a Th1 or Th2 lineage in terms of cytokine production patterns have not yet been fully elucidated. The authors have endeavored to study the role of the antigen in regulating the production of cytokines. To study this matter, a panel of antigens was chosen to include two random poly amino acids, PA1 (Poly(1-Phe, L-Glu)Poly-dL-Ala-PolyL-Lys), PA2 (Poly(Glu-NaAla), and two purified protein derivatives PPD1 (H37Rv virulent) and PPD2 (H37Ra non-virulent) obtained from WHO strains of Mycobacterium tuberculosis. After in vivo priming, murine spleen cells were prepared and three groups of cells (unfractionated, T cells, and CD4+ populations) were each separately stimulated in vitro with the original antigen Staphylococcal enterotoxin B (SEB) and phorbol myristate acetate (PMA). ELISA assays were subsequently performed on supernatants for IL-4, IL-5, IL-2 and IFN-g. The results indicate a different cytokine pattern for the various antigenic stimulations. The PPD1 induced IL-5 production, while the PPD2 induced high levels of IFN-gamma. SEB was shown to exert a strong effect on the cytokine profile shifting it towards a Th1-like profile. A comparison is made between the cytokine patterns in different cells. The role of antigens and superantigens in regulating cytokine production and determining the outcome of the pathological process in relation to other regulatory factors is discussed.

Effect of immunomodulators pyrimethamine and cimetidine on immunosuppression induced by sulfur mustard in mice.

Despite extensive world-wide research no effective therapy has been devised for the treatment and cure of patients exposed to sulfur mustard (S-M). A severe suppression of the immune system still remains the major cause of opportunist infections, septicemia and death in patients injured by S-M. In this report we present a model of S-M contamination in mice which is suitable for immunomodulation studies. Results show that differing doses of S-M caused an overall suppression of the immune response to SRBC as indicated by agglutination titers, (DTH) tests, spleen histology and spleen weight indices. In the second stage two immunomodulating agents; pyrimethamine and cimetidine were employed and their effectiveness in augmenting immune responses after S-M induced immunosuppression was evaluated. Pyrimethamine, at all doses employed, enhanced antibody titers to SRBC, augmented DTH responses, and restored splenic follicles as compared with controls only exposed to S-M. Cimetidine augmented antibody titers and enhanced DTH responses at doses of 10 and 15 mg/kg as compared with controls. At a dose of 5 mg/kg cimetidine did not exhibit any effect on titers or DTH responses. Histological studies revealed that cimetidine restored splenic follicles and increased macrophage numbers and phagocytic activity at all three doses. Spleen weight indices were not augmented by either drug. These data provide evidence that immunomodulating drugs may prove effective in countering the immunosuppressive effects of S-M.