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Cited by 357Parasitic Diseases Research and TreatmentParasites and Host InteractionsT-cell and B-cell Immunology

Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by Th3/Tr1-type cytokines IL-10 and transforming growth factor-β but not by a Th1 to Th2 shift

Doetze, Andrea, Satoguina, Judith, Burchard, Gerd, Rau, Thomas, Löliger, Cornelius, Fleischer, Bernhard, Hoerauf, Achim·2000·International Immunology
DOI 10.1093/intimm/12.5.623
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Abstract

Exposure to infective larvae of the filarial nematode Onchocerca volvulus (Ov) either results in patent infection (microfilaridermia) or it leads to a status called putative immunity, characterized by resistance to infection. Similar to other chronic helminth infections, there is a T cell proliferative hyporesponsiveness to Ov antigen (OvAg) by peripheral blood mononuclear cells (PBMC) from individuals with patent infection, i.e. generalized onchocerciasis (GEO), compared to PBMC from putatively immune (PI) individuals. In this study, mechanisms mediating this cellular hyporesponsiveness in GEO were investigated: the low proliferative response in PBMC from GEO individuals was associated with a lack of IL-4 production and significantly lower production of IL-5 compared to those from PI individuals, arguing against a general shift towards a T(h)2 response being the cause of hyporesponsiveness. In contrast, IL-10 and transforming growth factor (TGF)-beta, two cytokines associated with a T(h)3 response, seemed to mediate hyporesponsiveness: PBMC from individuals with GEO produced significantly more IL-10, and T cell proliferative hyporesponsiveness in this group could be reversed by the addition of anti-IL-10 and anti-TGF-beta antibodies. Hyporesponsiveness was specific for OvAg and not observed upon stimulation with related nematode antigens, arguing for a T cell-mediated, Ov-specific down-regulation. Ov-specific T cells could be cloned from GEO PBMC which have a unique cytokine profile (no IL-2 but high IL-10 and/or TGF-beta production), similar to the T cell subsets known to suppress ongoing inflammation (T(h)3 and T(r)1), indicating that this cell type which has not been found so far in infectious diseases may be involved in maintaining Ov-specific hyporesponsiveness.

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Crossref · 10.1093/intimm/12.5.623

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  • Lack of cellular response in helminth infections is associated with Th3/TR1 cell types producing IL-10 and TGF-β.

    “the lack of a cellular response in helminth infections has been associated with Th3/TR1 cell types that produce the anti-inflammatory cytokines IL-10 and transforming growth factor beta (TGF-␤) (125).”

    From Human and animal dirofilariasis: The emergence of a zoonotic mosaic (2012) · cites this paper as [125]

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Authors
Doetze, A., Satoguina, J., Burchard, G., Rau, T., Löliger, C., Fleischer, B., & Hoerauf, A.
Affiliations
Bernhard Nocht Institute for Tropical Medicine (DE)
Corresponding author
Doetze, Andrea
ORCID
Hoerauf, Achim
Venue
International Immunology
Publisher
Oxford University Press (OUP)
Published
2000-05
Volume
12
Issue
5
Pages
623-630
ISSN
  • 0953-8178 (ISSN-L)
  • 1460-2377
DOI
10.1093/intimm/12.5.623
OpenAlex
W2163569408
Cited by
357
References
42
Citations by year
2026: 5 · 2025: 3 · 2024: 3 · 2023: 9 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 6 · 2017: 7 · 2016: 3 · 2015: 16 · 2014: 12 · 2013: 7 · 2012: 20
FWCI
18.49
Type
journal article
Language
en
Open access
closed
Locations
  • International Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
onchocerciasis, Onchocerca volvulus, Th3 cells, Tr1 cells, IL-10, TGF-beta, Th1/Th2 shift, IL-4, IL-5, T cell proliferation, chronic helminth infection
MeSH terms
Animals, Antigens, Helminth, Cells, Cultured, Chronic Disease, Enzyme-Linked Immunosorbent Assay, T-Lymphocytes, Helper-Inducer, Humans, Immunity, Cellular, Leukocytes, Mononuclear, Onchocerciasis, T-Lymphocytes, Interleukin-4, Interleukin-5, T-Lymphocyte Subsets, Transforming Growth Factor beta, Interleukin-10, Onchocerca volvulus

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