Effect of age on concentrations of serum antibodies to viral, bacterial, and food antigens in elderly Swiss people.

Serum antibody concentrations to two viral, five bacterial, and two food antigens were investigated in 307 elderly Swiss subjects, and the hypothesis of whether serum antibody titers decreased with age was tested. The cross-sectional part of the study consisted of 216 unselected consecutive patients hospitalized in one geriatric hospital. The patients were divided into two age groups (65 to 84 and 85 to 102 years old), and their antibody titers were compared.

Food allergens transformed into tolerogens.

Antigen presentation determines immunologic outcome, and by modifying the presentation of allergen to the host one can prevent an allergic response. Under certain conditions, covalent linkage, of ovalbumin to rat IgG, a molecule already tolerated by the host, can make a protein-IgG conjugate which down-regulates the immune response to this food allergen. The suppression is allergen specific.

Induction of tolerance by administration of hapten-immunoglobulin conjugates is associated with decreased IL-2 and IL-4 production.

Intravenous administration of trinitrophenyl-modified isologous immunoglobulin-induced nonresponsiveness to subsequent epicutaneous painting of sensitizing doses of trinitrochlorobenzene. Isologous immunoglobulin with various degrees of trinitrophenyl substitution (11.2, 14.

Conjugates or dsDNA linked to human gammaglobulin inhibit anti-dsDNA antibodies in vitro.

Previous studies have shown that both nucleosides and oligonucleotides linked to isologous gammaglobulin suppress anti-nucleic acid antibody production both in vivo and in vitro. The aim of this study was to determine whether one can make a DNA-human gammaglobulin (HGG) conjugate which can inhibit anti-double stranded DNA (dsDNA) antibodies obtained from a heterogeneous population of systemic lupus erythematosus (SLE) sera. To do so, we constructed conjugates of sonicated dsDNA fragments of 100-400 base pairs covalently linked to HGG with varying degrees of substitution of DNA:HGG.

Prevention of allergic sensitization to beta-lactoglobulin with conjugates made of beta-lactoglobulin coupled to isologous immunoglobulin G.

We have shown that, under certain conditions, a single dose of a conjugate of beta-lactoglobulin linked to isologous IgG suppresses specific antibody responses (IgE, IgG, and IgA) in rats immunized with beta-lactoglobulin. This suppression is allergen specific. It also appears to be effective when animals are first immunized and then tolerized.

An intestinal galactose-specific lectin mediates the binding of murine IgE to mouse intestinal epithelial cells.

A number of lactose-binding lectins have recently been identified in the rat and mouse intestine, one of which corresponds to the C-terminal domain of IgE-binding proteins, originally identified in rat basophilic leukemia (RBL) cells and mouse 3T3 fibroblasts. In the present report, we describe the affinity purification of a rat intestinal lactose-specific lectin which binds murine IgE antibodies. This binding most likely occurs via the immunoglobulin carbohydrate chains, as it is inhibited by lactose.

Administration of a Tolerogen to Prevent Allergy.

A novel strategy to prevent an allergic immune response is presented. We tested the idea that a potent allergen such as cow's milk Beta lactoglobuline (βLG) can be rendered tolerogenic by covalent linkage to isologous gammaglobuline. We found that, under certain conditions, a single intravenous dose (of 2 mg) of βLG conjugated to rat gammaglobuline prevent both IgE and IgG antibodies to βLG.

A novel technique to link either proteins or peptides to gammaglobulin to construct tolerogens.

In order to extend the concept of constructing tolerogens (i.e., compounds which induce immunologic tolerance), we developed a novel method to covalently link either protein or peptide to isologous gammaglobulin.

Role of the thymus in natural tolerance to an autologous protein antigen.

C5-deficient mice grafted with thymus from C5-sufficient donors and immunized with C5 failed to make humoral antibody to C5, suggesting that the transfer of thymus had induced tolerance. Irradiated C5-deficient hosts repopulated with lymphoid cells from thymectomized C5-deficient mice grafted with C5-sufficient thymus also failed to respond to immunization with C5, thus showing that the state of tolerance can be adoptively transferred. These results demonstrate that natural tolerance to self-protein antigen is "learned" in the thymus.

Immunologic tolerance to DNA in B cell lines from both normal and autoimmune mice.

We examine whether B cell lines enriched for DNA specificity from either autoimmune (BWF1) or normal mice (Balb/c) can be rendered unresponsive to autoantigen in terms of the specific suppression of direct antibody-forming cells to DNA. These B cell lines were both Lyt-1 positive and negative. Preincubation with oligonucleotide, covalently linked to mouse gamma-globulin, specifically suppressed the antigen-driven response elicited by DNA horse red blood cells in B cell lines from both strains of mice.

Oligonucleotide linked to human gammaglobulin specifically diminishes anti-DNA antibody formation in cultured lymphoid cells from patients with systemic lupus erythematosus.

In vitro studies were undertaken to determine whether the level of anti-DNA antibody can be modulated in humans with systemic lupus erythematosus (SLE). DNA fragments of different sizes, i.e.

Mice naturally tolerant to C5 have T cells that suppress the response to this antigen.

We examined whether C5-sufficient mice which are naturally tolerant to this antigen have suppressor T cells to C5 humoral immune response. Two congenic strains of mice B10.D2 (NSN) and B10.

Immune response to nucleic acid antigens and native DNA by human peripheral blood lymphocytes in vitro.

The immunogenicity of DNA fragments (either oligonucleotide (oligo) or total DNA digest) covalently linked to keyhole limpet hemocyanin (oligo-KLH or DNA-KLH) was tested with peripheral blood lymphocytes (PBL) from 63 systemic lupus erythematosus patients (SLE) in vitro. PBL from 10 normal individuals and 11 rheumatoid arthritis (RA) patients served as controls. Antibodies to three nucleic acid antigens (oligo, denatured DNA (d-DNA), and native DNA (n-DNA] were assayed in supernatants of cultured lymphoid cells by a sensitive solid-phase radioimmunoassay.

HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis.

The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA-DR4 gene, which occurred with a frequency of 0.

Conjugation of DNA fragments to protein carriers by glutaraldehyde: immunogenicity of oligonucleotide-hemocyanin conjugates.

The practical realization of the concept of specific immunotherapy for systemic lupus erythematosus (SLE) has been hampered, thus far, by an inability to link DNA fragments to carrier protein. In this paper, a novel technique is described, in which glutaraldehyde is the linking agent. A 2-stage method was used to link oligonucleotides to a soluble protein carrier, such as keyhole limpet hemocyanin (KLH) or human gamma globulin (HGG), whereas a 1-stage technique was sufficient to link oligonucleotides to sheep red cells.

Influence of intravenous administration of nucleoside-coupled spleen cells on murine lupus nephritis in female (NZB X NZW)F1 mice.

In this study, we examine the influence of the intravenous administration of nucleoside-coupled spleen cells on the spontaneous development of murine lupus nephritis in young and adult BWF1 mice. In both age groups, this treatment failed to affect the autoimmune disease. Rather, in young mice administration of nucleoside-coupled spleen cells accelerates the appearance of anti-DNA antibody suggesting that BWF1 have a specific defect in the immunoregulation of anti-DNA antibody production.

Increased photosensitivity to near-ultraviolet light in murine SLE.

We investigated whether there is increased susceptibility to near-UVL in murine SLE. Cultured spleen cells from either strain of mice with lupus disease or conventional strains of mice were exposed to different UVL fractions in vitro. The effect of DNA synthesis, release, and repair was examined.

Anti-T cell antibody in juvenile rheumatoid arthritis.

One hundred-and-seven patients with juvenile rheumatoid arthritis (JRA) were studied for the presence or absence of an autoantibody in their sera directed against T cells. Using an indirect immunofluorescence technique on a fluorescence activated cell sorter, 71% of all patients were found to be positive on at least one sample. When studied according to the mode of onset of disease 75% of those with systemic onset, 70% with a pauciarticular, and 68% of those with a polyarticular onset were positive.