A B S T R A C T The effect of specific immunotherapy on several in vitro responses to ragweed antigen E has been evaluated in 17 atopic patients with ragweed hayfever. The methods employed were leukocyte histamine release, measurement of specific IgE anti-ragweed antibody and specific IgG anti-ragweed antibody, lymphocyte proliferation, and the production of two lymphocyte mediators (migration inhibitory factor and mitogenic factor). The duration of treatment and symptom improvement were also recorded for comparison.Immunotherapy was associated with a decrease in leukocyte sensitivity for histamine release to ragweed antigen E in a majority of the patients. In addition, there was a significant decrease in IgE anti-ragweed antibody and a significant increase in IgG anti-ragweed antibody. Immunotherapy also resulted in a significant decrease in lymphocyte responsiveness to ragweed antigen E as measured by proliferation and the production of mediators. Symptomatic improvement was best correlated with the presence of IgG anti-ragweed antibody responses. The production of this antibody was also associated with a decrease in lymphocyte responsiveness. The results of this study indicate that specific immunotherapy in ragweed-sensitive patients induces alterations in immunologic reactivity to ragweed antigen in vitro. This response is antigen specific, includes elements of both humoral and cellular immunity, and may account

A B S T R A C T The in vivo and in vitro responses to ragweed antigen E were evaluated in 28 untreated atopic patients with ragweed hayfever. The methods employed included direct skin testing, measurement of total serum IgE, measurement of specific IgE anti-ragweed antibodies, leukocyte histamine release, lymphocyte transformation, and release of lymphocyte mediators (migration inhibitory factor and mitogenic factor). The patients could be divided into sensitive and insensitive groups on the basis of their in vitro reactivity to antigen E. 20 patients in the sensitive group had statistically higher levels of total serum IgE, higher levels of specific IgE anti-ragweed antibodies, and greater leukocyte sensitivity as measured by antigen-induced histamine release than did eight patients in the insensitive group. Lymphocytes from sensitive patients produced greater amounts of migration inhibitory factor and mitogenic factor when challenged by antigen E than did lymphocytes from insensitive patients. A possible role for the lymphocyte in this allergic disease is discussed. serum IgE levels of paIgEAR levels but normal total serum IgE levels. Of interest was the finding that a small number of patients had diminished lymphocyte mediator production, histamine release, IgE, and IgEAR levels. One could not distinguish clinically between these two groups. METHODSPatients. 28 atopic patients with symptoms compatible with seasonal allergic rhinitis and no previous history of receiving ragweed immunotherapy were included in this study. The ages ranged from 15 to 64 yr (mean 28.9 yr) and included 23 males and 5 females. 18 nonatopic subjects served as controls.Skin tests. At one forearm site 0.05 ml of aqueous ragweed extract (100 protein nitrogen units/ml) alone was injected intradermally. In the opposite forearm 0.05 ml chlorpheniramine maleate (10 mg/ml) was injected before the subsequent intradermal injection of 0.05 ml ragweed extract at the same site. At a third site chlorpheniramine alone was injected (0.05 ml). The amount of erythema and induration were measured at each site at 15 min and 48 h. In one subject a punch biopsy specimen was obtained at 48 h from sites injected with ragweed extract plus chlorpheniramine and chlorpheniramine alone.Serum IgE levels. Serum samples were obtained from patients at the time of initial evaluation and IgE levels determined by use of a Phadebas kit purchased from Pharmacia (Uppsala, Sweden). Serum samples for IgE levels were also obtained from 50 subjects in the same age range as the patient population.Specific IgEAR levels. The radioallergosorbent test (RAST) was used to measure specific IgEAR levels (9). 10 ml of a 20% whole ragweed extract was conjugated to 500 mg of cyanogen bromide-activated cellulose particles (10). 25-, 50-, and 75-il samples of sera were added to 0.5-mg aliquots of the antigen-cellulose conjugate and incubated overnight in a horizontal rotator. After washing, 0.05 ml of "I-labeled immunosorbent purified anti-IgE (Fc) was added to each tube. The anti-IgE (...

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