Ultra-rush venom immunotherapy induces differential T cell activation and regulatory patterns according to the severity of allergy.
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.


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-gamma and IL-4 levels were assayed by ELISA, in whole-blood supernatants. IFN-gamma 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-gamma increased in whole blood when IL-4 decreased. Among T cells, the percentage of CD3+IFN-gamma+ 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-gamma 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.


CONCLUSIONS
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.
Mamessier
E
E
UPRES 3287, Université de la Méditerranée, and Service de Pneumo-allergologie, Hôpital Sainte Marguerite, Marseilles, France. liliemames@yahoo.fr
Birnbaum
J
J
Dupuy
P
P
Vervloet
D
D
Magnan
A
A
D000328:Adult; D000704:Analysis of Variance; D003888:Desensitization, Immunologic / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D016014:Linear Models; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014862:Wasp Venoms / Q000008:administration & dosage*
D015375:Receptors, Interleukin-2; D014862:Wasp Venoms; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma