1921
Volume 77, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Schistosomiasis mansoni is usually a chronic infection that leads to long-term, systemic exposure to schistosome antigens. Experimental infection is associated with immunoregulatory mechanisms, including T regulatory cells (Treg) that may help control morbidity and dampen resistance to re-infection. We now show that some schistosomiasis mansoni patients have high proportions of CD3/CD4/CD25 Treg. On effective treatment with praziquantel, these high Treg percentages decrease, and fewer of the remaining Treg express CD45RO. The proportion of Treg in –infected patients is inversely related to their percentage of activated, putative effector T cells (CD3/CD4/CD25/HLA-DR cells). We conclude some, but not all, schistosomiasis mansoni patients develop high percentages of circulating Treg, and effective treatment both decreases the levels of these cells and changes their phenotypes, possibly because of the removal of constant exposure to antigens from intravascular, egg-producing adult worms.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2007.77.676
2007-10-01
2017-09-25
Loading full text...

Full text loading...

/deliver/fulltext/14761645/77/4/0770676.html?itemId=/content/journals/10.4269/ajtmh.2007.77.676&mimeType=html&fmt=ahah

References

  1. Ross AG, Bartley PB, Sleigh AC, Olds GR, Li Y, Williams GM, McManus DP, 2002. Schistosomiasis. N Engl J Med 346 : 1212–1220.
  2. Gryseels B, Polman K, Clerinx J, Kestens L, 2006. Human schistosomiasis. Lancet 368 : 1106–1118.
  3. Goddard MJ, Jordan P, 1980. On the longevity of Schistosoma mansoni in man on St. Lucia, West Indies. Trans R Soc Trop Med Hyg 74 : 185–191.
  4. Butterworth AE, Fulford AJ, Dunne DW, Ouma JH, Sturrock RF, 1988. Longitudinal studies on human schistosomiasis. Philos Trans R Soc Lond B Biol Sci 321 : 495–511.
  5. Butterworth AE, Curry AJ, Dunne DW, Fulford AJ, Kimani G, Kariuki HC, Klumpp R, Koech D, Mbugua G, Ouma JH, Roberts M, Thiong’o FW, Capron A, Sturrock RF, 1994. Immunity and morbidity in human schistosomiasis mansoni. Trop Geogr Med 46 : 197–208.
  6. Dunne DW, Butterworth AE, Fulford AJ, Ouma JH, Sturrock RF, 1992. Human IgE responses to Schistosoma mansoni and resistance to re-infection. Mem Inst Oswaldo Cruz 87 (Suppl 4): 99–103.
  7. Webster M, Fallon PG, Fulford AJ, Butterworth AE, Ouma JH, Kimani G, Dunne DW, 1997. IgG4 and IgE responses to Schistosoma mansoni adult worms after treatment. J Infect Dis 175 : 493–494.
  8. Booth M, Shaw MA, Carpenter D, Joseph S, Kabatereine NB, Kariuki HC, Mwatha JK, Jones FM, Vennervald BJ, Ouma JH, Dunne DW, 2006. Carriage of DRB1*13 is associated with increased posttreatment IgE levels against Schistosoma mansoni antigens and lower long-term re-infection levels. J Immunol 176 : 7112–7118.
  9. Walter K, Fulford AJ, McBeath R, Joseph S, Jones FM, Kariuki HC, Mwatha JK, Kimani G, Kabatereine NB, Vennervald BJ, Ouma JH, Dunne DW, 2006. Increased human IgE induced by killing Schistosoma mansoni in vivo is associated with pretreatment Th2 cytokine responsiveness to worm antigens. J Immunol 177 : 5490–5498.
  10. Ganley-Leal LM, Mwinzi PN, Cetre-Sossah CB, Andove J, High-tower AW, Karanja DM, Colley DG, Secor WE, 2006. Correlation between eosinophils and protection against re-infection with Schistosoma mansoni and the effect of human immunodeficiency virus type 1 coinfection in humans. Infect Immun 74 : 2169–2176.
  11. Viana IR, Sher A, Carvalho OS, Massara CL, Eloi-Santos SM, Pearce EJ, Colley DG, Gazzinelli G, Correa-Oliveira R, 1994. Interferon-γ production by peripheral blood mononuclear cells from residents of an area endemic for Schistosoma mansoni. Trans R Soc Trop Med Hyg 88 : 466–470.
  12. Fitzsimmons CM, Joseph S, Jones FM, Reimert CM, Hoffmann KF, Kazibwe F, Kimani G, Mwatha JK, Ouma JH, Tukahebwa EM, Kariuki HC, Vennervald BJ, Kabatereine NB, Dunne DW, 2004. Chemotherapy for schistosomiasis in Ugandan fishermen: treatment can cause a rapid increase in interleukin-5 levels in plasma but decreased levels of eosinophilia and worm-specific immunoglobulin E. Infect Immun 72 : 4023–4030.
  13. Brown M, Mawa PA, Joseph S, Bukusuba J, Watera C, Whit-worth JA, Dunne DW, Elliott AM, 2005. Treatment of Schistosoma mansoni infection increases helminth-specific type 2 cytokine responses and HIV-1 loads in coinfected Ugandan adults. J Infect Dis 191 : 1648–1657.
  14. Joseph S, Jones FM, Walter K, Fulford AJ, Kimani G, Mwatha JK, Kamau T, Kariuki HC, Kazibwe F, Tukahebwa E, Kabatereine NB, Ouma JH, Vennervald BJ, Dunne DW, 2004. Increases in human T helper 2 cytokine responses to Schistosoma mansoni worm and worm-tegument antigens are induced by treatment with praziquantel. J Infect Dis 190 : 835–842.
  15. Mutapi F, Burchmore R, Mduluza T, Foucher A, Harcus Y, Nicoll G, Midzi N, Turner CM, Maizels RM, 2005. Praziquantel treatment of individuals exposed to Schistosoma haematobium enhances serological recognition of defined parasite antigens. J Infect Dis 192 : 1108–1118.
  16. Mduluza T, Ndhlovu PD, Midzi N, Scott JT, Mutapi F, Mary C, Couissinier-Paris P, Turner CM, Chandiwana SK, Woolhouse ME, Dessein AJ, Hagan P, 2003. Contrasting cellular responses in Schistosoma haematobium infected and exposed individuals from areas of high and low transmission in Zimbabwe. Immunol Lett 88 : 249–256.
  17. Mutapi F, Ndhlovu PD, Hagan P, Spicer JT, Mduluza T, Turner CM, Chandiwana SK, Woolhouse ME, 1998. Chemotherapy accelerates the development of acquired immune responses to Schistosoma haematobium infection. J Infect Dis 178 : 289–293.
  18. Woolhouse ME, Hagan P, 1999. Seeking the ghost of worms past. Nat Med 5 : 1225–1227.
  19. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M, 1995. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155 : 1151–1164.
  20. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA, 2001. CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167 : 1245–1253.
  21. Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH, 2001. Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med 193 : 1285–1294.
  22. Levings MK, Allan S, d’Hennezel E, Piccirillo CA, 2006. Functional dynamics of naturally occurring regulatory T cells in health and autoimmunity. Adv Immunol 92 : 119–155.
  23. Cavassani KA, Campanelli AP, Moreira AP, Vancim JO, Vitali LH, Mamede RC, Martinez R, Silva JS, 2006. Systemic and local characterization of regulatory T cells in a chronic fungal infection in humans. J Immunol 177 : 5811–5818.
  24. Baumgart M, Tompkins F, Leng J, Hesse M, 2006. Naturally occurring CD4+Foxp3+ regulatory T cells are an essential, IL-10-independent part of the immunoregulatory network in Schistosoma mansoni egg-induced inflammation. J Immunol 176 : 5374–5387.
  25. Taylor JJ, Mohrs M, Pearce EJ, 2006. Regulatory T cell responses develop in parallel to Th responses and control the magnitude and phenotype of the Th effector population. J Immunol 176 : 5839–5847.
  26. Singh KP, Gerard HC, Hudson AP, Reddy TR, Boros DL, 2005. Retroviral Foxp3 gene transfer ameliorates liver granuloma pathology in Schistosoma mansoni infected mice. Immunology 114 : 410–417.
  27. Mwinzi PN, Karanja DM, Colley DG, Orago AS, Secor WE, 2001. Cellular immune responses of schistosomiasis patients are altered by human immunodeficiency virus type 1 coinfection. J Infect Dis 184 : 488–496.
  28. Karanja DM, Hightower AW, Colley DG, Mwinzi PN, Galil K, Andove J, Secor WE, 2002. Resistance to re-infection with Schistosoma mansoni in occupationally exposed adults and effect of HIV-1 co-infection on susceptibility to schistosomiasis: a longitudinal study. Lancet 360 : 592–596.
  29. Ganley-Leal LM, Mwinzi PN, Cetre-Sossah CB, Andove J, High-tower AW, Karanja DM, Colley DG, Secor WE, 2006. Higher percentages of circulating mast cell precursors correlate with susceptibility to re-infection with Schistosoma mansoni. Am J Trop Med Hyg 75 : 1053–1057.
  30. Karanja DM, Colley DG, Nahlen BL, Ouma JH, Secor WE, 1997. Studies on schistosomiasis in western Kenya: I. Evidence for immune-facilitated excretion of schistosome eggs from patients with Schistosoma mansoni and human immunodeficiency virus coinfections. Am J Trop Med Hyg 56 : 515–521.
  31. Bayry J, Triebel F, Kaveri SV, Tough DF, 2007. Human dendritic cells acquire a semimature phenotype and lymph node homing potential through interaction with CD4+CD25+ regulatory T cells. J Immunol 178 : 4184–4193.
  32. Duggleby RC, Shaw TN, Jarvis LB, Kaur G, Gaston JS, 2007. CD27 expression discriminates between regulatory and non-regulatory cells after expansion of human peripheral blood CD4+ CD25+ cells. Immunology 121 : 129–139.
  33. Keever-Taylor CA, Browning MB, Johnson BD, Truitt RL, Bredeson CN, Behn B, Tsao A, 2007. Rapamycin enriches for CD4(+) CD25(+) CD27(+) Foxp3(+) regulatory T cells in ex vivo-expanded CD25-enriched products from healthy donors and patients with multiple sclerosis. Cytotherapy 9 : 144–157.
  34. Longhi MS, Hussain MJ, Mitry RR, Arora SK, Mieli-Vergani G, Vergani D, Ma Y, 2006. Functional study of CD4+CD25+ regulatory T cells in health and autoimmune hepatitis. J Immunol 176 : 4484–4491.
  35. Roncador G, Brown PJ, Maestre L, Hue S, Martinez-Torrecuadrada JL, Ling KL, Pratap S, Toms C, Fox BC, Cerundolo V, Powrie F, Banham AH, 2005. Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level. Eur J Immunol 35 : 1681–1691.
  36. Strauss L, Whiteside TL, Knights A, Bergmann C, Knuth A, Zippelius A, 2007. Selective survival of naturally occurring human CD4+CD25+Foxp3+ regulatory T cells cultured with rapamycin. J Immunol 178 : 320–329.
  37. Valencia X, Yarboro C, Illei G, Lipsky PE, 2007. Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol 178 : 2579–2588.
  38. Roederer M, 2001. Spectral compensation for flow cytometry: visualization artifacts, limitations, and caveats. Cytometry 45 : 194–205.
  39. Lühn K, Simmons CP, Moran E, Dung NT, Chau TN, Quyen NT, Thao le TT, Van Ngoc T, Dung NM, Wills B, Farrar J, Mc-Michael AJ, Dong T, Rowland-Jones S, 2007. Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue infection. J Exp Med 204 : 979–985.
  40. Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G, 2001. Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 193 : 1303–1310.
  41. Levings MK, Sangregorio R, Roncarolo MG, 2001. Human CD25(+)CD4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 193 : 1295–1302.
  42. Ko HS, Fu SM, Winchester RJ, Yu DT, Kunkel HG, 1979. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med 150 : 246–255.
  43. Eggena MP, Barugahare B, Jones N, Okello M, Mutalya S, Kityo C, Mugyenyi P, Cao H, 2005. Depletion of regulatory T cells in HIV infection is associated with immune activation. J Immunol 174 : 4407–4414.
  44. Butterworth AE, David JR, Franks D, Mahmoud AA, David PH, Sturrock RF, Houba V, 1977. Antibody-dependent eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: damage by purified eosinophils. J Exp Med 145 : 136–150.
  45. Yazdanbakhsh M, Tai PC, Spry CJ, Gleich GJ, Roos D, 1987. Synergism between eosinophil cationic protein and oxygen metabolites in killing of schistosomula of Schistosoma mansoni. J Immunol 138 : 3443–3447.
  46. Sakaguchi S, 2005. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6 : 345–352.
  47. Nishimura H, Honjo T, 2001. PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends Immunol 22 : 265–268.
  48. Blattman JN, Greenberg PD, 2006. PD-1 blockade: rescue from a near-death experience. Nat Immunol 7 : 227–228.
  49. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R, 2006. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439 : 682–687.
  50. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, DePierres C, Mncube Z, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJ, Klenerman P, Ahmed R, Freeman GJ, Walker BD, 2006. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443 : 350–354.
  51. Muhlbauer M, Fleck M, Schutz C, Weiss T, Froh M, Blank C, Scholmerich J, Hellerbrand C, 2006. PD-L1 is induced in hepa-tocytes by viral infection and by interferon-α and -β and mediates T cell apoptosis. J Hepatol 45 : 520–528.
  52. Smith P, Walsh CM, Mangan NE, Fallon RE, Sayers JR, Mc-Kenzie AN, Fallon PG, 2004. Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages. J Immunol 173 : 1240–1248.
  53. Colley DG, Sasser LE, Reed AM, 2005. PD-L2+ dendritic cells and PD-1+ CD4+ T cells in schistosomiasis correlate with morbidity. Parasite Immunol 27 : 45–53.
  54. Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S, Maeda M, Onodera M, Uchiyama T, Fujii S, Sakaguchi S, 2004. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol 16 : 1643–1656.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2007.77.676
Loading
/content/journals/10.4269/ajtmh.2007.77.676
Loading

Data & Media loading...

  • Received : 27 Apr 2007
  • Accepted : 25 Jun 2007

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error