Ultra-rush venom immunotherapy induces differential T cell activation and regulatory patterns according to the severity of allergy
Article first published online: 1 JUN 2006
Clinical & Experimental Allergy
Volume 36, Issue 6, pages 704–713, June 2006
How to Cite
Mamessier, E., Birnbaum, J., Dupuy, P., Vervloet, D. and Magnan, A. (2006), Ultra-rush venom immunotherapy induces differential T cell activation and regulatory patterns according to the severity of allergy. Clinical & Experimental Allergy, 36: 704–713. doi: 10.1111/j.1365-2222.2006.02487.x
- Issue published online: 1 JUN 2006
- Article first published online: 1 JUN 2006
- Submitted 4 November 2005; revised 17 January 2006; accepted 21 February, 2006
- regulatory T cells;
- Th1-to-Th2 switch;
- T lymphocytes;
- vespid venom
Background Venom immunotherapy (VIT) induces immune tolerance to hymenoptera venom antigens in allergic patients and is therefore a helpful model for studying modulation of allergic immune response. The objectives were to assess the early effects of ultra-rush VIT on T lymphocyte activation and regulatory profile induction, in all subjects combined and according to the four severity grades of the Mueller classification.
Materials and Methods Blood samples from 30 vespid-allergic patients were taken before and after the first day of treatment, and before day 15 and day 45 booster injections. IFN-γ and IL-4 levels were assayed by ELISA, in whole-blood supernatants. IFN-γ and IL-13-producing T cells, but also natural CD4+CD25+high regulatory T cells and acquired regulatory T cell proportions were assessed by flow cytometry. Results were analysed in the whole population and compared between patients with I–II or III–IV allergic reactions.
Results During VIT, IFN-γ increased in whole blood when IL-4 decreased. Among T cells, the percentage of CD3+IFN-γ+ cells increased while IL-13-producing T cells decreased. Proportions of CD4+CD25+high cells and IL-10-producing T cells increased with VIT. In I–II subjects, IFN-γ increased gradually, whereas it remained at low levels in III–IV patients. By contrast, IL-4 decrease was more pronounced in III–IV patients. Increase in CD4+CD25+high T cells occurred early in I–II patients but was delayed in III–IV patients. IL-10-producing T cells increased gradually in both groups but were in a lower proportion in III–IV patients.
Conclusion A T helper type 2 (Th2)-to-Th1 switch occurs during ultra-rush VIT, in parallel with natural and acquired regulatory T cell increase. These events occur earlier and at a higher level in less severe subjects, suggesting that VIT tolerance induction is easier to achieve in these patients.