title: Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection.
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.
authors: 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, Brazil; and.
authors: Pedro H
authors: PH
authors: Gazzinelli-Guimarães
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Sandra
authors: S
authors: Bonne-Année
authors: Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; and.
authors: Ricardo T
authors: 0000-0002-4713-575X
authors: RT
authors: Fujiwara
authors: Department of Immunology and Biochemistry, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.
authors: Helton C
authors: 0000-0002-5695-8256
authors: HC
authors: Santiago
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; tnutman@niaid.nih.gov.
authors: Thomas B
authors: 0000-0001-6887-4941
authors: TB
authors: Nutman
mesh_terms: D000485:Allergens / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005368:Filariasis / Q000276:immunology*; D006801:Humans
chemical_list: D000485:Allergens; D000953:Antigens, Protozoan