Differential effect of anti-B7-1 and anti-M150 antibodies in restricting the delivery of costimulatory signals from B cells and macrophages

Institute of Microbial Technology, Chandigarh, India.
The Journal of Immunology (Impact Factor: 4.92). 03/1998; 160(3):1067-77.
Source: PubMed


B7-1 and M150 are potent costimulatory molecules expressed on B cells and macrophages. We have examined the capacity of Abs against B7-1 and M150 in differentially inhibiting the costimulatory signals delivered by macrophages and B cells to OVA-specific CD4+ T cells. The anti-B7-1 Ab significantly blocked the proliferation of Th cells, MLR, T cell help to B cells, and secretion of IFN-gamma when B cells were used to provide costimulation, but not when macrophages were used. In contrast, anti-M150 Ab significantly decreased the proliferation of Th cells, MLR, and production of IFN-gamma, when macrophages were utilized to provide costimulatory signals, but not when B cells were used as APC. However, when macrophages activated with IFN-gamma were used as a source of costimulation, like anti-M150 Ab, Ab to B7-1 also down-regulated the activation of Th cells. The significance of this finding is that M150 is a potent first costimulatory signal for initiating proliferation and secretion of IFN-gamma and providing cognate help for B cells by Th cells when the macrophage is used as an accessory cell. M150-induced IFN-gamma production induces the expression of B7-1 on the surface of macrophages, which then delivers a second cosignal for Th cells. B7-1 works efficiently when B cell provides cosignal. Both of the molecules promote Th1 activity, as evidenced by the inhibition of the secretion of IFN-gamma but not IL-4 by Th cells with anti-M150 and B7-1 Abs.

Download full-text


Available from: Susmit Suvas, Apr 08, 2015
15 Reads
  • Source
    • "Reaction was stopped by adding 50 μl of 3 N H 2 SO 4 to wells. After this, optical density of each well was determined by ELISA reader (BioTek, USA) at 490 nm [29] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Incorporation of parasite's subcellular fractions in subunit vaccines can be a possible approach for formulation of vaccine against malaria. In this study, the immunogenicity and protective efficacy of 10,000g fraction of blood stage Plasmodium berghei was evaluated in mouse model. This fraction induced higher levels of anti parasite antibodies and provided complete and long lasting protection as compared to whole parasite antigens. Antiserum raised against it was immunoadsorbed on CNBr activated sepharose-4B to elute antigens from this fraction. Eluted antigens were characterized electrophoretically, and after lyophilization these were designated as ML-I (having 55, 64, 66, 74kDa proteins), ML-II (having 51, 64, 66, 72kDa proteins) and ML-III (having only 47kDa protein) sub-fractions. Mice were immunized with these sub-fractions and immune responses induced by various immunization regimens were evaluated and compared with that of 10,000g fraction. These sub-fractions imparted partial protection except ML-III, which was non-protective. 10,000g fraction as a whole provided complete protection and generated significantly higher level of IL-2 and IFN-γ in immune mice. ML-I produced significant amount of IL-1 and IL-4 as compared to ML-II. Enhanced level of malaria-specific IgG1 was produced by ML-II, but IgG2a was significantly higher in ML-I immunized mice. Conclusively, this study identifies 10,000g fraction as a promising blood stage vaccine candidate and suggests that a vaccine based upon multiple antigens may be more efficacious as compared to single antigen based formulations.
    Parasitology International 10/2012; 62(3). DOI:10.1016/j.parint.2012.10.002 · 1.86 Impact Factor
  • Source
    • "Reaction was stopped by adding 50 ll of 3 N H 2 SO 4 to wells. After this, optical density (OD) of each well was determined by ELISA reader (Dynatech Micro-reader 11) set to 490 nm (Agrewala et al. 1998). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Progress towards a vaccine against malaria is advancing rapidly with several candidate antigens being tested for their safety and efficacy. In present investigation, two polypeptides (43 and 48 kDa) of Plasmodium berghei (NK-65) were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Immunogenicity and protective efficacy of both these polypeptides formulated in saponin has been compared in Balb/c mice against challenge infection with P. berghei. Antibody responses were evaluated by indirect fluorescent antibody test and enzyme-linked immunosorbent assay. Merozoite invasion inhibition assay and challenge infections revealed that 48 kDa antigen is better immunogen as compared to 43 kDa and provide better protection against rodent malaria infection.
    Journal of parasitic diseases 10/2010; 34(2):68-74. DOI:10.1007/s12639-010-0012-5
  • Source
Show more