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1
*
INSERM U167, and
U416 Institut Pasteur de Lille, France;
Department of Microbiology, University of Western Australia;
§
Lab. Traitement de Données, Centre O. Lambret, Lille, France; and
¶
Department of Medicine, University of Cincinnati, Cincinnati, OH 45221
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-
mRNA expression, and frequency of
IFN--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-.
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