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Y Borel

Publications and source records attributed to Y Borel.

89 records · Page 5Linked to original sources

Carrier-induced tolerance to nucleic acid antigens.

BALB/c and SJL mice were treated with nucleosides-IgG1 as a tolerogen, before either primary or secondary immunization with nucleosides-keyhole limpet hemocyanin. Nucleoside-specific responses were measured serologically by a modified Farr assay, with either 14C-labeled denatured DNA or nucleosides-131-I-labeled BSA as test antigen. Specificity of the response was tested by hapten inhition experiments. Multiple doses of nucleosides-IgG1 tolerogen given before the primary or secondary immunization effectively suppressed the secondary and tertiary anti-nucleoside responses. The tolerogen did not suppress the response to an unrelated hapten-KLH conjugate. The IgG alone did not suppress the anti-nucleoside response of BALB/c mice to nucleosides-KLH. Single doses of tolerogen before the primary or secondary immunization were less effective. Residual antibody in partially suppressed BALB/c mice showed changes in specificity as compared to controls. Suppression of the secondary response of SJL mice was measured much more readily by binding of nucleosides-131-I-BSA than by binding of denatured DNA. This reflected an altered specificity of the residual antibody; in control animals, antibodies were directed against all four nucleosides, whereas the antibodies of partially suppressed animals were directed only against guanosine. Suppression of anti-nucleic acid antibody responses may have therapeutic application in the management of systemic lupus erythematosus.

Animals↗

Prevention of murine lupus nephritis by carrier-dependent induction of immunologic tolerance to denatured DNA.

Four nucleosides were covalently bound to isogeneic mouse immunoglobulin G (IgG) and injected into New Zealand mice. Mice that received the tetranucleoside isogeneic IgG from birth to 5 months of age failed to make antibody to denatured DNA. In contrast, mice that were similarly treated with tetranucleoside bovine serum albumin or tetranucleoside free of carrier produced the same amount of antibody to denatured DNA as did untreated mice of this strain. Mice that were rendered tolerant to denatured DNA by tetranucleoside isogeneic IgG failed to develop the chronic membranous glomerulonephritis that characterizes the renal lesions in animals of this strain.

Adenosine↗

Deletion of hapten-binding cells by a highly radioactive 125-I conjugate.

Exposure of normal mouse spleen cells in vitro to highly (125)I-labeled dinitrophenyl (DNP)-protein carrier conjugates specifically inactivated cells able to mount an immune response to that hapten after in vivo challenge. The deletion was hapten specific and independent of the radioactive carrier to which the hapten was bound. DNP-binding cells were inactivated by radioactivity that was not part of the hapten, but was solely confined to the carrier moiety. The deletion of the anti-DNP response lasted 2-3 wk and could be specifically inhibited.

Animals↗

Nonantigenicity and immunologic tolerance: the role of the carrier in the induction of tolerance to the hapten.

Treatment of adult mice with dinitrophenyl (DNP) bound to isogeneic serum resulted in a specific inability to respond to DNP after challenge with DNP-keyhole limpet hemocyanin (KLH) in complete Freund's adjuvant. The unresponsiveness to the hapten had all the characteristics of immunologic tolerance: it had a definite induction time; it was transient but could be maintained by additional injections of the tolerogen; it was antigen specific and dose dependent. In addition, the induction of tolerance to DNP is dependent on the nature of the carrier. Two main conclusions can be drawn from these data: DNP conjugates of three homopolymers of lysine were found to be nonimmunogenic in mice, yet tolerogenic. Thus, antigenicity is not necessary to induce tolerance. Among the various carriers tested, isogeneic 7S immunoglobulin (IgG) was found to be the most effective to induce and maintain tolerance to the hapten. This suggests that IgG may have a function other than its usual role as an immunoglobulin.

Animals↗

In vitro studies of the suppression of delayed hypersensitivity by the induction of partial tolerance.

Suppression of delayed hypersensitivity in vivo is correlated in vitro with the absence of macrophage migration inhibition in the presence of the antigen used to induce partial tolerance. The suppression of delayed hypersensitivity is antigen-specific in vivo as well as in vitro. The lymphocytes, and not the macrophages, are the cells involved in the induction of tolerance in terms of delayed hypersensitivity which is characterized by an absence of migratory factor activity.

Animals↗

Selective suppression of delayed hypersensitivity by the induction of immunologic tolerance.

Administration of DNP-BGG to newborn guinea pigs resulted, in more than half of the animals, in the specific suppression of delayed hypersensitivity to DNP-BGG and BGG, as shown after immunization with DNP-BGG in complete Freund's adjuvant. In contrast, all animals formed antibodies to DNP-BGG, whether or not delayed hypersensitivity to this antigen was present. No difference in antibody titers was found between pretreated and control animals. All animals had antibodies reacting specifically to the hapten DNP, and most of them to the carrier protein BGG, whether or not delayed hypersensitivity to the carrier protein was present. Furthermore, some animals with and without positive 24 hr skin test to DNP-BGG had antibodies with a combined hapten-carrier protein specificity to this antigen, i.e., a specificity which is similar to that of delayed hypersensitivity. Thus, delayed hypersensitivity and antibody formation to similar antigenic determinant were differently affected by injection of antigen in the neonatal period. The finding that delayed hypersensitivity and antibody formation could be dissociated by the induction of immunologic tolerance supports the assumption that delayed hypersensitivity and antibody formation are different immune processes which are not necessarily linked together.

Anaphylaxis↗

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. It affects both T and B cell immune responses. Administration of allergens linked to isologous IgG may provide a novel strategy for allergy prevention.

Allergens↗