IgE class-restricted tolerance induced by neonatal administration of soluble or cell-bound IgE. Cellular mechanisms.

Abstract

Unraveling the pathophysioiogy of IgE-mediated allergic disorders requires a thorough understanding of the complex mechanisms that control IgE antibody synthesis. The selective activation and further maturation of the IgE B cell are regulated by both antigen-specific and non-antigen-specific, but isotype-restricted, T cells and the soluble factors that they produce (1-6). Although the manner by which antigen-specific and isotype-restricted regulatory events are coordinated is still unresolved, studies of Ishizaka and colleagues (7-13) and of our group (14-19) indicate that the Fc determinants of IgE and the correspondingly specific Fc receptors for IgE (FcR~) ~ on lymphocytes contribute significantly to such regulatory mechanisms.IgE antibody responses can be significantly enhanced in experimental animals in which sensitization with antigen has been properly correlated with nonspecific perturbations such as low dose irradiation or treatment with immunosuppressive drugs (13,(20)(21)(22)(23). Similar perturbations, perhaps resulting from common respiratory virus infections (15), could be responsible for development of high IgE responses in individuals exposed to allergens over a sustained period of time (21), and are probably involved in the enhanced IgE production that accompanies parasite infections (22). Certain of the experimentally induced perturbations in normal mechanisms controlling IgE antibody responses can be selectively reversed by in vivo administration of biologically active soluble factors, obtained from body fluids of living animals (23). This is publication number 34 from the

Neonatal IgE Injections Do Not Modify <i>Nippostrongylus brasiliensi</i><i>s</i>-lnduced and Mercuric Chloride-Induced IgE Increase in the Rat

“…Several ex planations can be put forward to explain this discre pancy. The suggested down regulation of IgE re sponses by T-suppressive cells observed in mice by Chen and Katz [9] and Chen et al [10] could be absent in our two models as a result of the very strong effect of the stimulations. These stimulations could drasti cally increase the T-helper function and entirely mask a weak T-suppressive function.…”

“…A stim ulation similar to that used by Chen and Katz [9] and Chen et al [10] on the high IgE-responder BN rat strain resulted in a weak increase of serum IgE level (2 jug/ml) which is much lower than the IgE levels shown in tables I and II for Nb-infected LOU/C rats and HgCh-intoxicated BN rats.…”

“…The experiments of Chen and Katz [9] and Chen et al [10] demonstrated a polyclonal and long-lasting IgE tolerance induced by neonatal IgE injection. However, these authors only measured specific IgE.…”

“…In the studies performed by Chen and Katz [9] and Chen et al [10], the effect of neonatal IgE administra tion was tested on specific IgE responses induced in mice with aluminium hydroxyde as adjuvant. A stim ulation similar to that used by Chen and Katz [9] and Chen et al [10] on the high IgE-responder BN rat strain resulted in a weak increase of serum IgE level (2 jug/ml) which is much lower than the IgE levels shown in tables I and II for Nb-infected LOU/C rats and HgCh-intoxicated BN rats.…”

“…Autoregulation mechanisms by serum IgE via Fc£R-bearing lymphocytes have been described in the rat [1], mouse [2,3] and man [4][5][6][7][8], Moreover, Chen and Katz [9] and Chen et al [10] obtained an IgE class-restricted tolerance in mice neonatally treated by IgE injections.…”