The proposed experiments will test using patient lymphocytes, a model for immunoregulation that has been developed in schistosome and T. cruzi infected mice. We have found that a specific oligosaccharide, lacto-N- fucopentaose III (LNFPIII) stimulates B220+ cells from schistosome or T. cruzi infected mice, to proliferate and produce elevated levels of IL-10 and PGE2. These two molecules are known to down-regulate Th1 cell function and thus, our observations may partially explain the observed Th1 and Th2 shift that occurs in schistosome infected mice. We will also investigate the regulatory role of sugars on """"""""Adhesion' molecules. Schistosome infected patients have levels of slCAM-1 which are significantly elevated over non-infected controls. IL-10 has been shown to alter levels of ICAM-1 in vivo, and LNFPII, which elicits IL-10 and anti-LNFPIII antibodies, is found on LFA-1, the ligand for ICAM-1. Therefore, we will investigate whether the response to sugars, either anti-LNFPIII antibodies, or IL-10 production, also alters levels of ICAM- 1. We will determine if ICAM-1 is involved in granuloma formation, and how the lymphocyte response to oligosaccharides may alter this response. Lastly, in conjunction with Project 1, we will determine if titers of antibodies to LNFPIII or LNT, or B cell production of IL-10 and/or PGE2, correlates with patient clinical status, intensity of infection or HLA Class II type.
The specific aims of this proposal are:> 1) To test if patient lymphocytes respond to LNFPIII or other oligosaccharides, via the production of IL_10, prostaglandin E2 (PGE2); 2) To examine if specific oligosaccharides influence lymphocyte responses to other schistosome antigens; 3) To compare the roles oligosaccharide versus peptide moieties play in CD4+ T cell subset regulation and granuloma formation and in vitro; 4) To examine whether specific oligosaccharides or anti- LNFPIII antibodies are involved in production and release of slCAM-1 from patient cells in vitro; 5) To determine if adhesion molecules influence murine or patient in vitro granuloma formation; 6) To perform a correlative analysis with results from Specific Aims 1-5 with clinical status and HLA Class II type obtained in Project 1.
| Magalhaes-Santos, Isis F; Lemaire, Denise C; Andrade-Filho, Antonio S et al. (2003) Antibodies to Schistosoma mansoni in human cerebrospinal fluid. Am J Trop Med Hyg 68:294-8 |
| Braga, M D; Coelho, I C; Pompeu, M M et al. (1998) [Control of canine visceral leishmaniasis: comparison of results from a rapid elimination program of serum-reactive dogs using an immunoenzyme assay and slower elimination of serum-reactive dogs using filter paper elution indirect immunofluorescence] Rev Soc Bras Med Trop 31:419-24 |
