Search

Thirty-four out of 119 human T cell clones established from tonsillar or peripheral blood T cell suspensions of 3 nonallergic individuals were able to induce normal B cells to synthesize remarkable amounts of IgE in vitro. The activity of these clones was apparently mediated by triggering of the monomorphic molecular complex CD3 immediately before or during their incubation with the target B cells. The addition to the cultures of mitogen-stimulated autologous unfractionated T cells inhibited in a dose-dependent fashion, the T cell clone induced IgE, but not IgG, synthesis.

The IgE helper function of human T cell clones or their phytohemagglutinin-induced supernatants was positively correlated with their ability to produce or their content in interleukin 4 (IL-4), whereas it was inversely correlated with production of or content in gamma interferon. The addition to B cell cultures of anti-IL-4 antibody abolished not only the IgE synthesis induced by recombinant human IL-4, but also that induced by IL-4-producing T cell clones or their phytohemagglutinin-induced supernatants. A clonal analysis in nonatopic donors and patients with common atopy showed that atopics possess in their peripheral blood significantly higher numbers of T cells able to secrete IL-4 and to provide helper function for IgE.

Sera from 46 patients with malignant melanoma (MM) in different clinical stages and from 25 healthy blood donors were studied by an indirect conventional immunofluorescent technique (IIT) and by an immunofluorescent complement-fixation test (ICFT). No specific and reliable serological reactivity could be demonstrated against autologous and homologous MM and other nonmalignant pigmented tissues. An increased incidence of diffused antinuclear (ANA; 41%) and cytoplasmic epidermal cell autoantibodies (A-CYT; 71%) was observed in the patients by IIT. Statistical evaluation of the results gave significant values in the chi 2 test in patients for ANA (chi 2 = 5.2061; p less than 0.05) and for A-CYT (chi 2 = 8.9176; p less than 0.01) versus age-matched controls. Thyroid microsomal, gastric parietal cell, smooth muscle and mitochondria autoantibodies were, respectively, detected in 4.3, 4.3, 4.3 and 0% of patients' sera.

The central role of IgE antibodies in allergic bronchial asthma (ABA) is not disputed any longer. Immunological mechanisms other than IgE-mediated reactions in the pathogenesis of ABA have not yet been definitely demonstrated. There is controversy as to whether IgG STS antibodies, probably IgG4, play a role in the disease process. There is no evidence to support the involvement of immune complexes. Anti-beta-2-adrenergic receptor autoimmune responses cannot be considered as responsible for the development of the disease at the present time. In the last few years a great effort has been made to understand the immunological mechanisms underlying the enhanced and long-standing IgE antibody production in atopic diseases. The results obtained in different laboratories, including our own, are in favor of a high responder status to allergen epitopes in a large proportion of atopics and suggest that a preferential expression of IgE isotype in the antibody responses may occur through different mechanisms. Of great interest is the recent demonstration of IgE-binding factors with IgE-potentiating and suppressive activity and of other related regulatory molecules and receptors. Progress has been recently achieved in the characterization of mediators responsible for the different pathological changes of ABA. A linkage between immediate IgE-mediated reactions, bronchial late-phase reactions (LPR) and chronic inflammation (CI) has been reported. It has been demonstrated that a cascade of mediators and cell interactions induce both LPR and CI. There is evidence of a close relationship between LPR-CI and nonspecific bronchial hyperreactivity. A better knowledge of pathogenetic mechanisms of ABA would open new perspectives in the therapy. A modulation of IgE antibody production can be attempted in different ways. At present a control of mediator release and of airway hyperreactivity can be achieved by several pharmacological interventions and by the avoidance of common and/or occupational allergens or pollutants.

Factor I (fibrinogen) and factor VIII were shown, by an indirect immunofluorescence technique, to be present in human washed platelets. In the case of fibrinogen, the immunofluorescent pattern had a 'clod distribution' up to a 1:128 dilution of the antiserum. Factor VIII showed a 'speckled' pattern up to the 1:64 dilution. Cross-absorption studies confirmed the presence of such factors. Factor II, VII, IX, X and XIII, however, were not found in washed platelets. A diffuse fluorescence was noted using normal rabbit sera, but this was due to a cross-reaction, since it disappeared using a 1:32 diluted sera.

In the last 5 years some models of human IgE production in vitro have been investigated in our laboratory. Spontaneous IgE synthesis was found in cultures of B cells from most patients with atopic dermatitis or atopic patients with multiple sensitivities and from some patients with pollenosis, but only during the pollination period. A small and variable increase of the spontaneous IgE synthesis was induced by soluble factor(s) produced by T cells from patients with severe atopy. Selected helper T cell clones were also able to induce IgE synthesis in vitro by both atopic and normal B cells.