The house dust mite allergen, Dermatophagoides pteronyssinus, promotes type 2 responses by modulating the balance between IL-4 and IFN-gamma

• Published in: The Journal of immunology (1950) Vol. 160; no. 5; pp. 2456 - 2462
• Main Authors: Comoy, E E, Pestel, J, Duez, C, Stewart, G A, Vendeville, C, Fournier, C, Finkelman, F, Capron, A, Thyphronitis, G
• Format: Journal Article
• Language: English
• Published: United States 01.03.1998
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - physiology; AIDS/HIV; Allergens - administration & dosage; Allergens - drug effects; Allergens - immunology; Animals; Antigens, Dermatophagoides; Cysteine Endopeptidases - immunology; Cysteine Proteinase Inhibitors - pharmacology; Female; Glutathione Transferase - administration & dosage; Glutathione Transferase - immunology; Glycoproteins - administration & dosage; Glycoproteins - antagonists & inhibitors; Glycoproteins - immunology; Immunization; Immunoglobulin Isotypes - biosynthesis; Injections, Subcutaneous; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Mice; Mice, Inbred BALB C; Mites - immunology; RNA, Messenger - biosynthesis; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.5.2456

A common property of allergens is their potential to generate type 2 cytokine responses. To understand the mechanisms involved in this phenomenon, we have evaluated the polarizing potential of a major allergen, Dermatophagoides pteronyssinus 1 (Der p 1), in an heterologous immunization system using the glutathione S-transferase of the parasite Schistosoma mansoni (Sm28-GST) as immunogen. In previous studies, we showed that immunization with the Sm28-GST emulsified in CFA induced a nonpolarized immune response. In contrast, when alum was used as adjuvant, a type 2 immune response was induced against Sm28-GST. Using this experimental model, we examined whether the administration of Der p 1 together with Sm28-GST influenced the nonpolarized and/or the Th2 profiles induced by the CFA or the alum immunization, respectively. Our results showed that the introduction of Der p 1 in the CFA immunization protocol was associated with diminished anti-Sm28-GST IgG2a Ab titers, reduced IFN-gamma mRNA expression, and frequency of IFN-gamma-producing cells. In contrast, the introduction of Der p 1 in the alum protocol did not affect IL-4 or Ig isotype responses. The effect of Der p 1 was specific, since coimmunization with tetanus toxin fragment C did not affect the profile of the response against Sm28-GST. Furthermore, inactivation of Der p 1 reduced its ability to modify the immune response profile, suggesting that its protease activity played an important role in deviating the immune response. Our results suggest that the Der p 1 has the ability to modify the profile of an immune response by modulating the balance between the polarizing cytokines IL-4 and IFN-gamma.