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Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection

Gazzinelli-Guimarães, Pedro H, Bonne-Année, Sandra, Fujiwara, Ricardo T, Santiago, Helton C, Nutman, Thomas B·2016·The Journal of Immunology
DOI 10.4049/jimmunol.1600829PMC PMC5026971
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Abstract

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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Metadata

Authors
Gazzinelli-Guimarães, P. H., Bonne-Année, S., Fujiwara, R. T., Santiago, H. C., & Nutman, T. B.
Affiliations
  • National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892
  • Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais , Belo Horizonte 31270-901,
  • Department of Immunology and Biochemistry, Biological Sciences Institute, Federal University of Minas Gerais , Belo Horizonte 31270-901,
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2016-10-01
Volume
197
Issue
7
Pages
2772-2779
ISSN
  • 0022-1767
  • 1550-6606
DOI
10.4049/jimmunol.1600829
PMC
PMC5026971
Cited by
15
References
2
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)

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CoChat. (2026). Citation check: Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection. https://app.cochat.ai/papers/10.4049/jimmunol.1600829
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Gazzinelli-Guimarães, P. H., Bonne-Année, S., Fujiwara, R. T., Santiago, H. C., & Nutman, T. B. (2016). Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1600829