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J C Guery

Publications and source records attributed to J C Guery.

12 recordsLinked to original sources
PubMed2006

Understanding the oestrogen action in experimental and clinical atherosclerosis.

Whereas hormone replacement/menopause therapy (HRT) in postmenopausal women increases the coronary artery risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of oestradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favours an anti-inflammatory effect in vitro (cultured cells), it rather elicits in vivo a proinflammation at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. Endothelium is another important target for E2, as it potentiates endothelial NO and prostacyclin production, thus promoting the beneficial effects as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appears to be involved in the atheroprotective effect of E2. E2 also accelerates endothelial regrowth, thus favouring vascular healing. Finally, most of these effects of E2 are mediated by oestrogen receptor alpha, and are independent of oestrogen receptor beta. In summary, a better understanding of the mechanisms of oestrogen action not only on the normal and atheromatous arteries, but also on innate and adaptive immune responses is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective oestrogen receptor modulators.

Animals↗
PubMed1997

Impaired antigen presentation by murine I-Ad class II MHC molecules expressed in normal and HLA-DM-defective human B cell lines.

The inability of certain antigen processing mutant cell lines to present intact proteins to T cells and to form SDS-stable MHC class II dimers has been shown to result from defective expression of HLA-encoded DMA and DMB genes. We have utilized some of these mutants to determine species compatibility of antigen presentation components. Mouse MHC class II I-Ad cDNA was transfected into the human B cell lymphoblastoid cell lines 8.1.6, 7.9.6 (a mutant cell line derived from 8.1.6) and an independent deletion mutant T2 (called 8.1.6d, 7.9.6d and T2.d respectively). These cells were than examined for various functions in antigen presentation. Interestingly, none of the cells transfected with I-Ad presented peptides derived from intact proteins to specific T cell hybridomas. However, presentation of synthetic peptides by these cells was normal. The ability to form SDS-stable dimers was dramatically reduced in the transfectants. In addition, I-Ad molecules at the cell surface appeared loaded predominantly with the invariant chain peptides, CLIP. These properties of the I-Ad transfectants are identical to those described for HLA class II molecules expressed in HLA-DM mutants. Perhaps the most interesting finding was the inability of I-Ad in 8.1.6 to present protein antigens. Since 8.1.6 cells present antigens to HLA-DR, DP, DQ-restricted T cells and also have intact HLA-DM and invariant chain (II) functions, these results argue that some component of human antigen processing machinery is incompatible with I-Ad molecules.

Animals↗
PubMed1996

Selective development of T helper (Th)2 cells induced by continuous administration of low dose soluble proteins to normal and beta(2)-microglobulin-deficient BALB/c mice.

Continuous administration of soluble proteins, delivered over a 10-d period by a mini-osmotic pump implanted subcutaneously, induces a long-lasting inhibition of antigen-specific T cell proliferation in lymph node cells from BALB/c mice subsequently primed with antigen in adjuvant. The decreased T cell proliferative response is associated with a down-regulation of the T helper cell (Th)1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma and with a strong increase in the secretion of the Th2 cytokines IL-4 and IL-5 by antigen specific CD4+ T cells. This is accompanied by predominant inhibition of antigen-specific antibody production of IgG2a and IgG2b, rather than IgG1 isotype. Interestingly, inhibition of Th1 and priming of Th2 cells is also induced in beta(2) microglobulin-deficient BALB/c mice, indicating that neither CD8+ nor CD4+ NK1.1+ T cells, respectively, are required. The polarization in Th2 cells is stably maintained by T cell lines, all composed of CD4+/CD8- cells expressing T cell receptor for antigen (TCR) alpha/beta chains, derived from BALB/c mice treated with continuous antigen administration, indicating that they originate from Th2 cells fully differentiated in vivo. This polarization is induced in BALB/c mice by continuous administration of any protein antigen tested, including soluble extracts from pathogenic microorganisms. Priming of Th2 cells is dose dependent and it is optimal for low rather than high doses of protein. Blocking endogenous IL-4 in vivo inhibits expansion of antigen-specific Th2 cells, but does not restore IFN-gamma production by T cells from mice treated with soluble antigen-specific Th2 cells, but does not restore IFN-gamma production by T cells from mice treated with soluble antigen, indicating the involvement of two independent mechanisms. Consistent with this, Th2 cell development, but not inhibition of Th1 cells, depends on non-major histocompatibility complex genetic predisposition, since the Th2 response is amplified in BALB/c as compared to DBA/2, C3H, or C57BL/6 mice whereas tested. These findings support the hypothesis that continuous release of low amounts of protein antigens from pathogenic microorganisms may polarize the immune response toward a Th2 phenotype in susceptible mouse strains.

Animals↗
PubMed1994

Failure to demonstrate long-lived MHC saturation both in vitro and in vivo. Implications for therapeutic potential of MHC-blocking peptides.

Peptides that bind with high affinity to class II MHC molecules can inhibit T cell activation both in vitro and in vivo. Thus, they have been suggested as potential therapeutic agents for MHC-associated autoimmune diseases. We have constructed nonnatural peptides with high affinity for certain disease-associated MHC alleles. More specifically, a particular peptide, designated as CY-760.50, was found to have a high binding affinity for DR1, slow dissociation kinetics after binding to MHC, and prolonged stability in human serum. However, when the ability of this peptide to block peptide presentation to an influenza hemagglutinin 307-319 peptide-specific, DR1-restricted T cell clone was examined, it was found that MHC blockade could only be achieved when high concentrations of peptide were present along with Ag in the fluid phase. Thus, pretreatment of APC with MHC class II blocker, followed by removal of unbound blocker, did not result in saturation of MHC molecules, because practically immediate reacquisition of Ag-presenting capacity was observed after removal of fluid phase blocker. The pharmacokinetic behavior and the duration of blocking activity of CY-760.50 were also examined in vivo, taking advantage of the fact that the mouse MHC class II molecule I-Ab also bound CY-760.50 with high affinity. CY-760.50 administered i.v. to C57BL/6 mice was rapidly cleared from the circulation and virtually undetectable in the serum 10 min after injection. This fast clearance rate was paralleled by a similarly short duration of the MHC blockade effect. These in vivo results have implications concerning the biology of peptide-MHC interactions, and suggest that MHC blockade may not be feasible as a therapeutic approach unless effective concentrations of inhibitor can be maintained over extended periods of time in the extracellular fluids.

Amino Acid Sequence↗
PubMed1994

Characteristics of polyreactive and monospecific IgG anti-laminin autoantibodies in the rat mercury model.

Brown-Norway (BN) rats injected with HgCl2 produce anti-laminin antibodies responsible for an autoimmune glomerulonephritis. The properties of three IgG1 monoclonal antibodies (mAb) previously obtained in this model, and of immunoglobulins eluted from kidneys of diseased rats, were compared in the present study. Two mAb (Hg15 and Hg16) recognized laminin only, while the third one (Hg17) was polyreactive, as were some of the kidney-eluted immunoglobulins; they reacted with laminin and with several other antigens including 2,4,6-trinitrophenyl (TNP). The Hg17 mAb and kidney-eluted polyreactive antibodies were affinity purified using a TNP-bovine serum albumin (BSA) column; their affinity for TNP was high (2 x 10(-8)M, and 1 x 10(-8)M, respectively) but less than that of a TNP-specific (LO-DNP-2) mAb (2 x 10(-11) M). The Hg17 mAb and kidney-eluted antibodies reacted more effectively with TNP28-BSA than with TNP8.5-BSA, while the TNP-specific mAb reacted equally well with both conjugates. The Hg17 mAb was the most cationic (pI: 7) of the anti-laminin mAb and this was even more evident when F(ab')2 fragments were studied (pI: 8.2). The polyreactive kidney-eluted immunoglobulins that bound TNP were also more cationic (pI: 7.4-9.3) than the fraction that did not recognize TNP (pI: 5.8-8.6). The anti-laminin mAb bound in vivo to the glomerular basement membrane, but only the Hg17 mAb could be eluted with DNP alone. This study shows that polyreactive anti-laminin antibodies are produced during this autoimmune disease, and indicates that they may have pathogenic potential.

Animals↗
PubMed1991

Effect of the thiol group on experimental gold-induced autoimmunity.

Brown Norway rats injected with aurothiopropanolsulfonate sodium salt develop systemic autoimmunity. The aim of this study was to assess the influence of the sulfur-containing group in this experimental model of gold-induced autoimmunity. It was shown that the sulfur-containing group does not induce autoimmunity of itself, but potentiates the immunotoxic effects of gold.

Animals↗
PubMed1991

Experimental gold-induced autoimmunity.

The pathogenesis of gold-induced autoimmunity and membranous glomerulopathy is not well understood. HgCl2 and D-penicillamine, other chemicals known to trigger membranous glomerulopathy in humans, induce autoimmune manifestations in Brown-Norway (BN) rats but not in Lewis (LEW) rats. These chemicals trigger T-cell clones which are specific for self class II molecules from the major histocompatibility complex and are probably responsible for the polyclonal B-cell activation observed. The aim of this work was to test the effects of aurothiopropanolsulphonate (ATPS) in BN and LEW rats. In BN rats, ATPS induced a polyclonal B-cell activation marked by lymphoproliferation, hyperimmunoglobulinaemia affecting mainly IgE, and by the production of numerous autoantibodies. A glomerulonephritis occurred, initially due to anti-glomerular basement membrane antibody deposition, and later to the formation of granular deposits, occasionally resulting in a typical membranous glomerulopathy. Self class-II-specific T-cells were found that might be responsible for the polyclonal B-cell activation. Lewis rats were free of glomerulopathy but, like BN rats, exhibited an interstitial nephritis and some degree of polyclonal B-cell activation. These findings demonstrate that, depending on the strain, ATPS triggers different B-cell clones inducing different degrees of autoimmunity.

Animals↗