CHARACTERIZATION OF PROLIFERATIVE RESPONSES AND CYTOKINE MESSENGER-RNA PROFILES INDUCED BY VESPULA VENOM IN PATIENTS WITH SEVERE REACTIONS TO WASP STINGS

The reasons why severe allergic reactions to bee and wasp stings devel op in only a small portion of exposed individuals are incompletely und erstood, but differences in T cell responses to venom antigens compari ng allergic and non-allergic individuals are likely to be important. T o identify such differences, venom-induced proliferative responses and cytokine mRNA production by blood mononuclear cells from Vespula veno m-allergic patients and non-allergic individuals were compared. Mononu clear cells from most venom-allergic patients proliferated in response to alkylated Vespula venom (7275 +/- 8387 ct/min, n = 19), and the ex tent of proliferation was greater for patients with a history of multi ple prior stings and those with high levels of venom-specific IgE. Alt hough mononuclear cells from non-allergic subjects showed little or no proliferation in response to venom (926 +/- 711 ct/min, n = 8), produ ction of mRNAs coding for IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma) in response to Vespula venom by cells from non-allergic s ubjects was detected by reverse transcriptase-polymerase chain reactio n (RT-PCR), indicating that these individuals had been previously sens itized to venom antigens. In contrast to the Th0 cytokine mRNA profile observed for non-allergic individuals, venom-allergic patients releas ed a more restricted profile of cytokines following stimulation with v enom. Only IFN-gamma mRNA expression was detected in all individuals e valuated, whereas IL-2 mRNA was net detected during the first 48 h of stimulation, and T cells from only one of three venom-allergic individ uals produced detectable IL-4 or IL-5 mRNA. The difference in cytokine profiles observed comparing venom-allergic patients and non-allergic controls could not be attributed to intrinsic differences in T cells f rom these individuals, because polyclonal stimulation with phorbol myr istate acetate (PMA) + ionophore induced similar cytokine mRNA profile s in the two groups. These studies demonstrate clear differences in th e T cell responses of venom-allergic subjects, that may contribute to the development of severe allergic reactions in these individuals.