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Background: Recognition of antigen bound to the major histocompatibility complex by the T cell receptor is insufficient to lead to T cell proliferation and effector function, which require co-stimulatory signals, such as those resulting from the interaction of CD28 expressed on T lymphocytes and CD80/CD86 expressed on APCs. Lack of interaction between these accessory molecules during antigen stimulation leads to a state of antigen-specific lymphocyte unresponsiveness. Previous studies have shown that rush venom immunotherapy decreases venom-specific T cell proliferation very early after the initiation of the rush., Objective: In order to see whether this hyporeactivity was associated with a down regulation of accessory molecules, we studied CD28 surface expression on T lymphocytes from 10 non-atopic controls and from 10 non-atopic patients undergoing rush venom immunotherapy., Methods: Peripheral blood samples were collected before the rush (day 0), at the end of the rush (day 1), at day 15 and at day 45. CD28 expression was analysed using flow cytometry with double labelling of the CD4+ and CD8+ lymphocyte subpopulations., Results: At baseline CD28 was expressed at a higher level on T lymphocytes from allergic patients than from control subjects (P < 0.04) and in particular on the CD8 subset (P < 0.01), reflecting a decrease in the suppressive CD8+CD28- subpopulation. No changes were found in the percentages of total CD28+ T cells, CD4+CD28+ or CD8+CD28+ cells at the different time points after the initiation of of immunotherapy., Conclusion: These results suggest that the CD28 pathway is probably involved in the development of allergic reactions, but at least at the phenotypic level, CD28 expression remained unchanged after rush venom immunotherapy.

The mechanism by which specific immunotherapy exerts its beneficial effect remains unclear. In order to evaluate the influence of venom immunotherapy on the T-cell cytokine pattern of allergic reactions, we studied interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA expression of peripheral T lymphocytes from 12 patients undergoing rush venom desensitization, before treatment at Day 0 (D0), at Day 15 (D1 5) and Day 90 (D90) after treatment, and from seven controls. Antigen-specific T-ceIl proliferation was also determined. Cytokine mRNA expression was evaluated using in situ hybridization, 24 hr after culture of peripheral T cells with medium, venom, or an unrelated allergen. Allergene-induced T-cell proliferation decreased at D15 and D90 of rush immunotherapy (P ≤ 0.02). In venom-stimulated cultures of the patient group, there was a decrease in IL-4 mRNA-positive cells at D15 and D90 (P C 0001). Before desensitization, IFN-γ mRNA expression was lower in patients than in controls and did not increase after in vitro allergen stimulation. In contrast, after immunotherapy, spontaneous IFN-γ mRNA expression increased, but only at D90 (P ≤ 0.001). The cytokine pattern observed at D90 after immunotherapy was similar to that observed in control subjects. In conclusion, venom immunotherapy induced an altered cytokine mRNA pattern in allergen-stimulated T cells which was dissociated from the early changes of allergen-induced T-cell responsiveness. [ABSTRACT FROM AUTHOR]