Presented at:
2006 Annual Meeting of the American Academy of Allergy, Asthma and Immunology
Miami, FL, March 3-7, 2006
Induction of IL-10 Occurs Early and Precedes Serum IgG Blocking Activity During a Cluster Regimen of Grass Pollen Immunotherapy
Wilcock LK, Francis JN, Paraskavopoulos G, Till SJ, Durham SR
Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, UK
Rationale: Allergen immunotherapy results in IL-10-associated T-cell regulation and production of IgG ‘blocking’ antibodies (Nouri-Aria, K. J Immunol 2004;172:3252-9). This study aimed to establish the onset and time-course of these regulatory mechanisms during grass immunotherapy.
Methods: Blood was obtained before and two weekly during a 6-8 week updosing ‘Cluster’ regimen of grass pollen immunotherapy (n=12) (Alutard SQ Phleum Pratense) and thereafter monthly/quarterly during 12 months maintenance injections. Serum allergen-specific (Phleum pratense) IgG4 was measured by ELISA. Flow cytometry was used to detect serum inhibitory activity for IgE-facilitated CD23-dependent allergen binding to B-cells. Allergen-driven IL-10 was assessed by ELISA of PBMC culture supernatants at 6 days .Late phase skin responses at 24 hr after intra-dermal allergen (10BU, Phleum pratense) provided a clinical readout of tolerance induction.
Results: A reduction in the late skin response occurred within 2 weeks (p=0.009) which corresponded to an increase in PBMC IL-10 production (p=0.001). These changes occurred at low allergen doses (approximately 3,300 SQ, compared to monthly maintenance 100,000 SQ injections). Increases in IgG4 (p=0.01) and in IgG serum inhibitory activity (p=0.001) occurred later, at 4-6 weeks after commencing treatment.
Conclusion: The appearance of regulatory mechanisms during grass pollen immunotherapy occurs as early as 2 weeks during the updosing phase. IL-10, a cellular marker of tolerance, precedes increases in IgG4 production and IgG-associated serum inhibitory activity. Early production of IL-10 may therefore make an important contribution to the induction of humoral tolerance during immunotherapy.