{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:30:05Z","timestamp":1778661005677,"version":"3.51.4"},"reference-count":55,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,6]]},"abstract":"<jats:p>Immunoregulation is considered a common feature of <jats:italic>Schistosoma mansoni<\/jats:italic> infections, and elevated levels of T regulatory (Treg) lymphocytes have been reported during chronic human schistosomiasis. We now report that the removal of Treg (CD4+\/CD25<jats:sup>hi<\/jats:sup>\/CD127<jats:sup>low<\/jats:sup> lymphocytes) from peripheral blood mononuclear cells (PBMCs) of <jats:italic>S. mansoni<\/jats:italic>\u2013infected individuals leads to increased levels of phytohemagglutinin (PHA)-stimulated interferon gamma (IFN\u03b3) production and decreased interleukin-10 (IL-10) responses. Exposure to schistosome antigens did not result in measurable IFN\u03b3 by either PBMC or Treg-depleted populations. Interleukin-10 responses to soluble egg antigens (SEA) by PBMC were unchanged by Treg depletion, but the depletion of Treg greatly decreased IL-10 production to soluble worm antigenic preparation (SWAP). Proliferative responses to PHA increased upon Treg removal, but responses to SEA or SWAP did not, unless only initially low responders were evaluated. Addition of anti-IL-10 increased PBMC proliferative responses to either SEA or SWAP, but did not alter responses by Treg-depleted cells. Blockade by anti-transforming growth factor-beta (TGF-\u03b2) increased SEA but not SWAP proliferative responses by PBMC, whereas anti-TGF-\u03b2 increased both SEA- and SWAP-stimulated responses by Treg-depleted cultures. Addition of both anti-IL-10 and anti-TGF-\u03b2 to PBMC or Treg-depleted populations increased proliferation of both populations to either SEA or SWAP. These studies demonstrate that Treg appear to produce much of the antigen-stimulated IL-10, but other cell types or subsets of Treg may produce much of the TGF-\u03b2. The elevated levels of Treg seen in chronic schistosomiasis appear functional and involve IL-10 and TGF-\u03b2 in antigen-specific immunoregulation perhaps leading to regulation of immunopathology and\/or possibly decreased immunoprotective responses.<\/jats:p>","DOI":"10.4269\/ajtmh.17-0966","type":"journal-article","created":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T07:00:35Z","timestamp":1524553235000},"page":"1770-1781","source":"Crossref","is-referenced-by-count":19,"title":["Functional Studies of T Regulatory Lymphocytes in Human Schistosomiasis in Western Kenya"],"prefix":"10.4269","volume":"98","author":[{"given":"Bartholomew N.","family":"Ondigo","sequence":"first","affiliation":[{"name":"Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;"},{"name":"Department of Biochemistry and Molecular Biology, Egerton University, Nakuru, Kenya;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric M.","family":"Ndombi","sequence":"additional","affiliation":[{"name":"Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;"},{"name":"Department of Pathology, Kenyatta University, Nairobi, Kenya;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah C.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John K.","family":"Oguso","sequence":"additional","affiliation":[{"name":"Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Carter","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nupur","family":"Kittur","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Evan","family":"Secor","sequence":"additional","affiliation":[{"name":"Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana M. S.","family":"Karanja","sequence":"additional","affiliation":[{"name":"Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel G.","family":"Colley","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia;"},{"name":"Department of Microbiology, University of Georgia, Athens, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Lancet","first-page":"2253","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014"},{"key":"b2","series-title":"PLoS Negl Trop Dis","first-page":"e0004306","article-title":"FOXP3+ regulatory T cells in hepatic fibrosis and splenomegaly caused by Schistosoma japonicum: the spleen may be a major source of Tregs in subjects with splenomegaly","volume":"10","author":"Romano","year":"2016"},{"key":"b3","series-title":"J Infect Dis","first-page":"1792","article-title":"Posttreatment changes in cytokines induced by Schistosoma mansoni egg and worm antigens: dissociation of immunity- and morbidity-associated type 2 responses","volume":"209","author":"Wilson","year":"2014"},{"key":"b4","series-title":"PLoS One","first-page":"e16860","article-title":"Regulatory and activated T cells in human Schistosoma haematobium infections","volume":"6","author":"Nausch","year":"2011"},{"key":"b5","series-title":"J Infect Dis","first-page":"835","article-title":"Increases in human T helper 2 cytokine responses to Schistosoma mansoni worm and worm\u2010tegument antigens are induced by treatment with praziquantel","volume":"190","author":"Joseph","year":"2004"},{"key":"b6","series-title":"Trans R Soc Trop Med Hyg","first-page":"514","article-title":"Human schistosomiasis mansoni: intensity of infection differentially affects the production of interleukin-10, interferon-gamma and interleukin-13 by soluble egg antigen or adult worm antigen stimulated cultures","volume":"98","author":"Silveira","year":"2004"},{"key":"b7","series-title":"Infect Immun","first-page":"4984","article-title":"Immunity after treatment of human schistosomiasis: association between cellular responses and resistance to reinfection","volume":"61","author":"Roberts","year":"1993"},{"key":"b8","series-title":"Clin Exp Immunol","first-page":"281","article-title":"Phenotypical characterization of regulatory T cells in humans and rodents","volume":"185","author":"Rodr\u00edguez-Perea","year":"2016"},{"key":"b9","series-title":"Immunol Cell Biol","first-page":"346","article-title":"Human FoxP3(+) CD4(+) regulatory T cells: their knowns and unknowns","volume":"89","author":"Miyara","year":"2011"},{"key":"b10","series-title":"Eur J Immunol","first-page":"1681","article-title":"Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level","volume":"35","author":"Roncador","year":"2005"},{"key":"b11","series-title":"Cell","first-page":"455","article-title":"Regulatory T cells: key controllers of immunologic self-tolerance","volume":"101","author":"Sakaguchi","year":"2000"},{"key":"b12","series-title":"PLoS Negl Trop Dis","first-page":"e0003995","article-title":"CD4+CD25hiFOXp3+ regulatory T cells and cytokine responses in human schistosomiasis before and after treatment with praziquantel","volume":"9","author":"Schmiedel","year":"2015"},{"key":"b13","series-title":"Am J Trop Med Hyg","first-page":"676","article-title":"T regulatory cell levels decrease in people infected with Schistosoma mansoni on effective treatment","volume":"77","author":"Watanabe","year":"2007"},{"key":"b14","series-title":"Eur J Immunol","first-page":"925","article-title":"Is FOXP3 a bona fide marker for human regulatory T cells?","volume":"38","author":"Roncarolo","year":"2008"},{"key":"b15","series-title":"J Immunol Methods","first-page":"41","article-title":"Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha chain (CD127), allowing consistent identification and sorting of live cells","volume":"319","author":"Hartigan-O\u2019Connor","year":"2007"},{"key":"b16","series-title":"PLoS Negl Trop Dis","first-page":"e637","article-title":"Influence of exposure history on the immunology and development of resistance to human Schistosomiasis mansoni","volume":"4","author":"Black","year":"2010"},{"key":"b17","series-title":"J Infect Dis","first-page":"272","article-title":"Circulating CD23+ B cell subset correlates with the development of resistance to Schistosoma mansoni reinfection in occupationally exposed adults who have undergone multiple treatments","volume":"199","author":"Mwinzi","year":"2009"},{"key":"b18","series-title":"Lancet","first-page":"592","article-title":"Resistance to reinfection with Schistosoma mansoni in occupationally exposed adults and effect of HIV-1 co-infection on susceptibility to schistosomiasis: a longitudinal study","volume":"360","author":"Karanja","year":"2002"},{"key":"b19","series-title":"Rev Inst Med Trop S\u00e3o Paulo","first-page":"397","article-title":"A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni","volume":"14","author":"Katz","year":"1972"},{"key":"b20","author":"WHO","year":"2013"},{"key":"b21","series-title":"Int Arch Allergy Immunol","first-page":"420","article-title":"Immune responses during human schistosomiasis mansoni: I. In vitro lymphocyte blastogenic responses to heterogeneous antigenic preparations from schistosome kggs, worms and cercariae","volume":"53","author":"Colley","year":"1977"},{"key":"b22","series-title":"J Exp Med","first-page":"488","article-title":"Delayed hypersensitivity-type granuloma formation and dermal reaction induced and elicited by a soluble factor isolated from Schistosoma mansoni eggs","volume":"132","author":"Boros","year":"1970"},{"key":"b23","series-title":"Eur J Immunol","first-page":"S116","article-title":"Regulatory T cells\u2014a brief history and perspective","volume":"37 (Suppl 1)","author":"Sakaguchi","year":"2007"},{"key":"b24","series-title":"FASEB J","first-page":"2253","article-title":"Naturally occurring regulatory T cells: markers, mechanisms, and manipulation","volume":"26","author":"Schmetterer","year":"2012"},{"key":"b25","series-title":"J Immunol Methods","first-page":"77","article-title":"Human immune compartment comparisons: optimization of proliferative assays for blood and gut T lymphocytes","volume":"445","author":"Dock","year":"2017"},{"key":"b26","series-title":"PLoS Negl Trop Dis","article-title":"Control of neglected tropical diseases in Burundi: partnerships, achievements, challenges, and lessons learned after four years of programme implementation","volume":"8","author":"Ndayishimiye","year":"2014"},{"key":"b27","series-title":"Am J Trop Med Hyg","first-page":"508","article-title":"Integrated implementation of programs targeting neglected tropical diseases through preventive chemotherapy: identifying best practices to roll out programs at national scale","volume":"86","author":"Hanson","year":"2012"},{"key":"b28","series-title":"BMC Med","first-page":"67","article-title":"Control of neglected tropical diseases needs a long-term commitment","volume":"8","author":"Zhang","year":"2010"},{"key":"b29","series-title":"Parasitology","first-page":"1719","article-title":"The schistosomiasis control initiative (SCI): rationale, development and implementation from 2002\u20132008","volume":"136","author":"Fenwick","year":"2009"},{"key":"b30","series-title":"Infect Immun","first-page":"23","article-title":"Effects of treatment on IgE responses against parasite allergen-like proteins and immunit to reinfection in childhood schistosome and hookworm coinfections","volume":"81","author":"De Moira","year":"2013"},{"key":"b31","series-title":"J Infect Dis","first-page":"159","article-title":"Integrated analysis of innate, Th1, Th2, Th17, and regulatory cytokines identifies changes in immune polarisation following treatment of human schistosomiasis","volume":"208","author":"Bourke","year":"2013"},{"key":"b32","series-title":"PLoS Pathog","first-page":"e1002171","article-title":"IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni","volume":"7","author":"Wilson","year":"2011"},{"key":"b33","series-title":"Trop Med Int Health","first-page":"431","article-title":"Associations between specific antibody responses and resistance to reinfection in a Senegalese population recently exposed to Schistosoma mansoni","volume":"12","author":"Vereecken","year":"2007"},{"key":"b34","series-title":"Parasite Immunol","first-page":"347","article-title":"Immunology of human schistosomiasis","volume":"36","author":"Colley","year":"2014"},{"key":"b35","series-title":"Braz J Med Biol Res","first-page":"171","article-title":"Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection","volume":"31","author":"Corr\u00eaa-Oliveira","year":"1998"},{"key":"b36","series-title":"J Infect Dis","first-page":"1474","article-title":"Immune responses induced by repeated treatment do not result in protective immunity to Schistosoma haematobium: interleukin (IL)-5 and IL-10 responses","volume":"186","author":"van den Biggelaar","year":"2002"},{"key":"b37","series-title":"Mem\u00f3rias do Inst","first-page":"95","article-title":"Immune response in different clinical groups of schistosomiasis patients","volume":"82 (Suppl 4)","author":"Gazzinelli","year":"1987"},{"key":"b38","series-title":"Am J Trop Med Hyg","first-page":"793","article-title":"Immune responses during human schistosomiasis. XII. Differential responsiveness in patients with hepatosplenic disease","volume":"35","author":"Colley","year":"1986"},{"key":"b39","series-title":"J Infect Dis","first-page":"1502","article-title":"Cytokine production in acute versus chronic human Schistosomiasis mansoni: the cross-regulatory role of interferon-gamma and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens","volume":"179","author":"Montenegro","year":"1999"},{"key":"b40","series-title":"Parasite Immunol","first-page":"345","article-title":"The effect of anti-IL-10 on proliferation and cytokine production in human schistosomiasis: fresh versus cryopreserved cells","volume":"20","author":"Grogan","year":"1998"},{"key":"b41","series-title":"Scand J Immunol","first-page":"393","article-title":"Cytokine regulation of human immune response to Schistosoma mansoni: analysis of the role of IL-4, IL-5 and IL-10 on peripheral blood mononuclear cell responses","volume":"46","author":"Malaquias","year":"1997"},{"key":"b42","series-title":"Eur J Immunol","first-page":"1399","article-title":"Evidence of a T helper type 2 activation in human schistosomiasis","volume":"26","author":"Ara\u00fajo","year":"1996"},{"key":"b43","series-title":"J Immunol","first-page":"4715","article-title":"Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity","volume":"156","author":"King","year":"1996"},{"key":"b44","series-title":"J Mol Cell Biol","first-page":"29","article-title":"TGF-\u03b2: the sword, the wand, and the shield of FOXP3(+) regulatory T cells","volume":"4","author":"Tran","year":"2012"},{"key":"b45","series-title":"J Immunol","first-page":"4654","article-title":"Segregated regulatory CD39+CD4+ T cell function: TGF-\u03b2-producing Foxp3- and IL-10-producing Foxp3+ cells are interdependent for protection against collagen-induced arthritis","volume":"187","author":"Kochetkova","year":"2011"},{"key":"b46","series-title":"J Immunother","first-page":"339","article-title":"CD4+CD25+ regulatory T cells that secrete TGF\u03b2 and IL-10 are preferentially induced by a vaccine vector","volume":"27","author":"Hussain","year":"2004"},{"key":"b47","series-title":"Int Immunol","first-page":"249","article-title":"IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells","volume":"16","author":"Zhang","year":"2004"},{"key":"b48","series-title":"Annu Rev Immunol","first-page":"99","article-title":"Transforming growth factor-beta regulation of immune responses","volume":"24","author":"Li","year":"2006"},{"key":"b49","series-title":"Parasitol Today","first-page":"18","article-title":"Maintaining the immunological balance in parasitic infections: a role for TGF-\u03b2?","volume":"16","author":"Omer","year":"2000"},{"key":"b50","series-title":"Microbes Infect","first-page":"1313","article-title":"TGF-beta in infections and infectious diseases","volume":"1","author":"Reed","year":"1999"},{"key":"b51","series-title":"J Allergy Clin Immunol","first-page":"984","article-title":"Interleukins (from IL-1 to IL-38), interferons, transforming growth factor \u03b2, and TNF-\u03b1: receptors, functions, and roles in diseases","volume":"138","author":"Akdis","year":"2016"},{"key":"b52","series-title":"J Infect Dis","first-page":"1207","article-title":"Interleukin 10 (IL-10)\u2013producing CD1dhi regulatory B cells from Schistosoma haematobium\u2013infected individuals induce IL-10\u2013positive T cells and suppress effector T-cell cytokines","volume":"210","author":"van der Vlugt","year":"2014"},{"key":"b53","series-title":"Nat Rev Immunol","first-page":"680","article-title":"Regulatory T cells: CD8+ TReg cells join the fold","volume":"10","author":"Leavy","year":"2010"},{"key":"b54","series-title":"Trans R Soc Trop Med Hyg","first-page":"952","article-title":"Immune responses and immunoregulation in relation to human schistosomiasis in Egypt. 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