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The journal of immunology : official journal of the American Association of Immunologists v.197 no.7, 2016년, pp.2772 - 2779   SCI SCIE
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Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection

Gazzinelli-Guimarães, Pedro H. (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 ) ; Bonne-Année, Sandra (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 ) ; Fujiwara, Ricardo T. (Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil ) ; Santiago, Helton C. (and ) ; Nutman, Thomas B. (Department of Immunology and Biochemistry, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil ) ;
  • 초록  

    Among the various hypotheses put forward to explain the modulatory influence of helminth infection on allergic effector responses in humans, the IL-10–induced suppression of Th2-associated responses has been the leading candidate. To explore this helminth/allergy interaction more fully, parasite- and allergen-specific CD4 + T cell responses in 12 subjects with filarial infections, and coincident allergic sensitization (filarial [Fil] + allergy [A] + ) were compared with the responses to three appropriate control groups (Fil − A − [ n = 13], Fil − A + [ n = 12], Fil + A − [ n = 11]). The most important findings revealed that Fil + A + had marked ( p < 0.0001 for all cytokines) increases in parasite Ag-driven Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), and the regulatory (IL-10) cytokines when compared with Fil + A − . Moreover, using multiparameter flow cytometry, filarial parasite Ag induced a marked increase in not only the frequency of CD4 + T cells producing IL-4, IL-5, IL-2, and TNF-α in Fil + A + when compared with Fil + A − patients, but also in the frequencies of polyfunctional Th2-like (CD4 + IL-4 + IL-5 + and CD4 + IL-2 + IL-4 + IL-5 + TNF-α + ) cells. The Th2-associated responses seen in the Fil + A + group were correlated with serum IgE levels ( p < 0.01, r = 0.5165 for IL-4; p < 0.001, r = 0.5544 for IL-5; and p < 0.001, r = 0.4901 for IL-13) and levels of circulating eosinophils ( p < 0.0116, r = 0.5656) and their degranulation/activation products (major basic protein [ p < 0.001, r = 0.7353] and eosinophil-derived neurotoxin [ p < 0.01, r = 0.7059]). CD4 + responses to allergen were not different (to a large extent) among the groups. Taken together, our data suggest that allergic sensitization coincident with filarial infection drives parasite Ag-specific T cell hyperresponsiveness, which is characterized largely by an augmented Th2-dominated immune response.


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