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Regulatory T Cells Limit Induction of Protective Immunity and Promote Immune Pathology following Intestinal Helminth Infection

Sawant, Deepali V, Gravano, David M, Vogel, Peter, Giacomin, Paul, Artis, David, Vignali, Dario A A·2014·The Journal of Immunology
DOI 10.4049/jimmunol.1202502PMC PMC3955731
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Abstract

Foxp3+ regulatory T cells (Tregs) have a well-characterized role in limiting autoimmunity and dampening deleterious immune responses. However, a potential consequence of the immunosuppressive function of Tregs can be the limitation of protective immunity to infectious pathogens. Parasitic infections are a potent stimulus for the generation of Treg responses, which may be beneficial to both the parasite and the host by promoting persistence of infection and limiting immune-mediated pathology, respectively. In this study, we explore the functional role of Tregs post–low-dose infection with the intestinal helminth parasite Trichuris muris, which yields a chronic infection because of inefficient induction of Th2 responses. Early Treg depletion postinfection resulted in expedited worm clearance, and was associated with reduced Th1-mediated inflammation of the intestinal environment. Interestingly, this protective immunity was lost, and worm burden enhanced if Tregs were depleted later once the infection was established. Early and late Treg depletion resulted in enhanced Th2 and reduced Th1 cytokine and humoral responses. Blockade of the Th2 cytokine IL-4 resulted in a moderate increase in Th1 but had no effect on worm burden. Our findings suggest that Tregs preferentially limit Th2 cell expansion, which can impact infections where clear immune polarity has not been established. Thus, the impact of Treg depletion is context and time dependent, and can be beneficial to the host in situations where Th1 responses should be limited in favor of Th2 responses.

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Research works printed but not linked: 25

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Metadata

Authors
Sawant, D. V., Gravano, D. M., Vogel, P., Giacomin, P., Artis, D., & Vignali, D. A. A.
Affiliations
  • Department of Immunology, St. Jude Children’s Research Hospital , Memphis, TN 38105
  • Department of Pathology, St. Jude Children’s Research Hospital , Memphis, TN 38105
  • Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2014-03
Volume
192
Issue
6
Pages
2904-2912
ISSN
  • 0022-1767
  • 1550-6606
DOI
10.4049/jimmunol.1202502
PMC
PMC3955731
Cited by
54
References
2
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)

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CoChat. (2026). Citation check: Regulatory T Cells Limit Induction of Protective Immunity and Promote Immune Pathology following Intestinal Helminth Infection. https://app.cochat.ai/papers/10.4049/jimmunol.1202502
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Sawant, D. V., Gravano, D. M., Vogel, P., Giacomin, P., Artis, D., & Vignali, D. A. A. (2014). Regulatory T Cells Limit Induction of Protective Immunity and Promote Immune Pathology following Intestinal Helminth Infection. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1202502