Vaccination with a multi-epitopic recombinant allergen induces specific immune deviation via T-cell anergy.
Prophylactic vaccination has recently emerged as a major paradigm toward the prevention and therapy of allergies and asthma; however, the immunological basis of this approach remains to be elucidated. We examined the potential and mechanism of prophylaxis of allergic response in B6D2F1 mice with a multi-epitopic recombinant allergen, rKBG8.3 (MERA-8.3), which represents a major group of allergens of grass pollens, used herein as a model of MERA vaccine. Vaccination (subcutaneous) with soluble MERA-8.3, prior to immunization with the MERA-8.3 in alum, led to suppression of the IgE antibody response and a concomitant increase in IgG2a antibody response specific to the MERA-8.3 in a dose-dependent manner. Analysis of cytokine patterns in spleen and lymph node cells revealed a marked decrease of interleukin-2 (IL-2) and IL-4 production and to a lesser extent a decrease of interferon-gamma (IFN-gamma) synthesis, resulting in an increased ratio of IFN-gamma: IL-4 in vaccinated-immunized mice compared with untreated-immunized control mice. Furthermore, splenocytes of mice treated with the MERA-8.3 alone proliferated to MERA-8.3 in vitro with reduced capacity compared with the splenocytes of MERA-8.3-alum immunized mice, owing to a markedly reduced level of IL-2 production in the former. Collectively, these results suggest that vaccination with the MERA-8.3 induces T-cell anergy, which is pivotal to deviation of specific immunity from Th2- to Th1-like, and may serve as an important approach to prevention and therapy of allergic disorders.
Cao
Y
Y
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Yang
M
M
Luo
Z
Z
Mohapatra
S S
SS
D000485:Allergens / Q000276:immunology*; D000818:Animals; D017635:Clonal Anergy / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D007376:Interleukin-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E