Skip to main content

Advertisement

SpringerLink
Log in

Demonstration of Low-Regulatory CD25High+CD4+ and High-Pro-inflammatory CD28−CD4+ T-Cell Subsets in Patients with Ulcerative Colitis: Modified by Selective Granulocyte and Monocyte Adsorption Apheresis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Low-CD25High+CD4+, a subset of regulatory CD25+CD4+ T cells and high-inflammatory CD28−CD4+ T cells can exacerbate ulcerative colitis (UC). This study sought to investigate the frequency of CD25High+CD4+ and CD28−CD4+ T cells in patients with UC and the changes in these cells during Adacolumn granulocyte and monocyte adsorption apheresis (GMA). Subjects were 12 patients with active UC, 11 with quiescent UC, and 14 healthy volunteers (HVs). The mean clinical activity index was 15.7 ± 2.2 in active UC and 4.5 ± 1.1 in quiescent UC. Peripheral blood samples were stained with CD4, CD25, and CD28 antibodies for flow cytometry. Patients with active UC received GMA and blood samples were examined before and after the first GMA session. Patients with active UC (P < 0.04) or quiescent UC (P < 0.02) had a higher percentage of CD28−D4+T cells compared with HVs, while the percentage of CD28+CD4+ T cells was lower in both UC groups compared with HVs (P = 0.03 and P < 0.02). Patients with active UC had a lower percentage of CD25High+CD4+T cells compared with quiescent UC patients (P < 0.001). A significant increase in CD25High+CD4+ T cells was associated with GMA (P < 0.03). Low CD25High+CD4+ and high CD28−CD4+ are prominent features in UC. The increase in CD25High+CD4+ T cells induced by GMA should contribute to improved immune function. Additional studies are warranted, since a low frequency of CD25High+CD4+ − and a high frequency of CD28−CD4+ − expressing T cells might be a predictor of clinical response to GMA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Isaacs KL, Lewis JD, Sandborn WJ (2005) State of the art: IBD therapy and clinical trials in IBD. Inflamm Bowel Dis 11:S3–S12

    Article  PubMed  Google Scholar 

  2. Kanai K, Watanabe M (2005) Clinical application of human CD4+CD25+ regulatory T cells for the treatment of inflammatory bowel disease. Expert Opin Biol Ther 5:451–462

    Article  PubMed  CAS  Google Scholar 

  3. Schmidt D, Goronzy JJ, Weyand CM (1996) CD4+CD7-CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J Clin Invest 97:2027–2037

    Article  PubMed  CAS  Google Scholar 

  4. Lenschow DJ, Walunas TL, Bluestone JA (1996) CD28/B7 system of T cell costimulation. Annu Rev Immunol 14:233–258

    Article  PubMed  CAS  Google Scholar 

  5. Martens P, Goronzy JJ, Schaid D (1997) Expansion of unusual CD4+ T cells in severe rheumatoid arthritis. Arth Rheum 40:1106–1114

    Article  CAS  Google Scholar 

  6. Markovic-Plese S, Cortese I, Wandinger KP (2001) CD4+CD28- costimulation-independent T cells in multiple sclerosis. J Clin Invest 108:1185–1194

    Article  PubMed  CAS  Google Scholar 

  7. De Tena JG, Manzano L, Leal JC (2004) Active Crohn’s disease patients show a distinctive expansion of circulating memory CD4+CD45RO+CD28null T cells. J Clin Immunol 24:185–196

    Article  Google Scholar 

  8. Gershon RK (1975) A disquisition on suppressor T cells. Transplant Rev 26:170–185

    PubMed  CAS  Google Scholar 

  9. Sakaguchi S, Sakaguchi N, Shimizu J (2001) Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 182:18–32

    Article  PubMed  CAS  Google Scholar 

  10. Curotto de Lafaille MA, Lafaille JJ (2002) CD4+ regulatory T cells in autoimmunity and allergy. Curr Opin Immunol 14:771–778

    Article  PubMed  CAS  Google Scholar 

  11. Annacker O, Pimenta-Araujo R (2001) CD25+CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10. J Immunol 166:3008–3018

    PubMed  CAS  Google Scholar 

  12. Saniabadi AR, Hanai H, Lofberg R (2003) Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher 7:48–59

    Article  Google Scholar 

  13. Kashiwagi N, Sugimura K, Koiwai H, Saniabadi A (2002) Immunomodulatory effects of granulocyte and monocyte adsorption apheresis as a treatment for patients with ulcerative colitis. Dig Dis Sci 6:1334–1341

    Article  Google Scholar 

  14. Shimoyama T, Sawada K, Hiwatashi N (2001) Safety and efficacy of granulocytes and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher 16:1–9

    Article  PubMed  CAS  Google Scholar 

  15. Suzuki Y, Yoshimura N, Saniabadi AR (2004) Selective granulocytes and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative colitis: a prospective uncontrolled study. Dig Dis Sci 49:565–571

    Article  PubMed  CAS  Google Scholar 

  16. Hanai H, Watanabe F, Takeuchi K (2003) Leukcocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective uncontrolled pilot study. Clin Gastroenterol Hepatol 1:28–35

    Article  PubMed  Google Scholar 

  17. Lichtiger S, Present DH, Kornbluth A (1994) Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 330:1841–1845

    Article  PubMed  CAS  Google Scholar 

  18. Saniabadi AR, Hanai H, Suzuki Y (2005) Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system: An adjunct or an alternative to drug therapy? J Clin Apher 20:171–184

    Article  PubMed  Google Scholar 

  19. Hiraishi K, Takeda Y, Shiobara N (2003) Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis. Ther Apher Dial 7:334–340

    Article  PubMed  Google Scholar 

  20. D’Arrigo C, Candal-Couto JJ, Greer M (1993) Human neutrophil Fc receptor-mediated adhesion under flow: a hollow fiber model of intravascular arrest. Clin Exp Immunol 100:173–179

    Article  Google Scholar 

  21. Kanke K, Nakano M, Hiraishi H (2004) Evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis. Dig Liv Dis 36:512–518

    Article  Google Scholar 

  22. Naganuma M, Funakoshi S, Sakuraba A (2004) Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflamm Bowel Dis 10:251–257

    Article  PubMed  Google Scholar 

  23. Yamamoto T, Umegae S, Kitagawa T (2004) Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study. Aliment Pharmacol Ther 20:783–792

    Article  PubMed  CAS  Google Scholar 

  24. Domenech E, Hinojosa J, Esteve-Comas M, Spanish Group for the Study of Crohn’s Disease and Ulcerative Colitis (GETECCU) (2004) Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther 20:1347–1352

    Article  PubMed  CAS  Google Scholar 

  25. Suzuki Y, Yoshimura N, Fukuda K, Shirai K, Saito Y, Saniabadi AR (2006) A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis. Dig Dis Sci Sep 27

  26. McCarthy DA, Rampton DS, Liu Y-C (1991) Peripheral blood neutrophils in inflammatory bowel disease: morphological evidence of in vivo activation in active disease. Clin Exp Immunol 86:489–493

    Article  PubMed  CAS  Google Scholar 

  27. Rugtveit J, Brandtzaeg P, Halstensen TS (1994) Increased macrophage subsets in inflammatory bowel disease:apparent recruitment from peripheral blood monocytes. Gut 35:669–674

    PubMed  CAS  Google Scholar 

  28. Meuret G, Bitzi A, Hammer B (1978) Macrophage turnover in Crohn’s disease and ulcerative colitis. Gastroenterology 74:501–503

    PubMed  CAS  Google Scholar 

  29. Brannigan AE, O’Connell PR, Hurley H (2000) Neutrophil apoptosis is delayed in patients with inflammatory bowel disease. Shock 13:361–366

    PubMed  CAS  Google Scholar 

  30. Cassatella MA (1995) The production of cytokines by polymorphonuclear neutrophils. Immunol Today 16:21–26

    Article  PubMed  CAS  Google Scholar 

  31. Nikolaus S, Bauditz J, Gionchetti P (1998) Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin-10 during intestinal inflammation. Gut 42:470–476

    Article  PubMed  CAS  Google Scholar 

  32. Mahida YR (2000) The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis 6:21–33

    Article  PubMed  CAS  Google Scholar 

  33. Hanauer SB (2006) Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 12:S3–S9

    Article  PubMed  Google Scholar 

  34. Allison MC, Dhillon AP, Lewis WG (eds) (1998) Inflammatory bowel disease. Mosby, London, pp 15–95

    Google Scholar 

  35. Tibble JA, Sigthorsson G, Bridger D (2000) Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 119:15–22

    Article  PubMed  CAS  Google Scholar 

  36. Limburg P, David M, Ahlquist A, Sandborn WJ (2000) Faecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhoea referred for colonoscopy. Am J Gastroenterol 95:2831–2837

    Article  PubMed  CAS  Google Scholar 

  37. Kuchroo V, Das MP, Brown JA (1995) B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 development pathways: application to autoimmune disease therapy. Cell 80:707–718

    Article  PubMed  CAS  Google Scholar 

  38. Lenschow DJ, Ho SC, Satter H (1995) Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. J Exp Med 181:1145–1155

    Article  PubMed  CAS  Google Scholar 

  39. Strober W, Fuss IJ, Blumberg RS (2002) The immunology of mucosal models of inflammation. Annu Rev Immunol 20:495–549

    Article  PubMed  CAS  Google Scholar 

  40. Karandikar NJ, Vanderlugt CL, Walunas T (1996) CTLA-4: a negative regulator of autoimmune disease. J Exp Med 184:783–788

    Article  PubMed  CAS  Google Scholar 

  41. Rulifson IC, Sperling AI, Fields PE, Fitch FW, Bluestone JA (1997) CD28 costimulation promotes the production of Th2 cytokines. J Immunol 158:658–665

    PubMed  CAS  Google Scholar 

  42. Shahinian A, Pfeffer KP, Lee TM (1993) Differential T cell costimulatory requirements in CD28-deficient mice. Science 261:609–612

    Article  PubMed  CAS  Google Scholar 

  43. Green JM, Noel PJ, Sperling AI (1994) Absence of B7-dependent responses in CD28-deficient mice. Immunity 1:501–508

    Article  PubMed  CAS  Google Scholar 

  44. Read S, Malmstom V, Powrie F (2001) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J Exp Med 192:295–302

    Article  Google Scholar 

  45. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25high regulatory cells in human peripheral blood. J Immunol 31:1247–1253

    Article  Google Scholar 

  46. Makita S, Kanai T, Oshima S (2004) CD4+CD25bright T cells in human intestinal lamia propria as regulatory cells. J Immunol 173:3119–3130

    PubMed  CAS  Google Scholar 

  47. Kashiwagi N, Sugimura K, Koiwai H, Saniabadi A (2002) Immunomodulatory effects of granulocyte and monocyte adsorption apheresis as a treatment for patients with ulcerative colitis. Dig Dis Sci 6:1334–1341

    Article  Google Scholar 

  48. Andoh A, Tsujikawa T, Inatomi O, Deguchi Y, Hata K, Kitoh K, Sasaki M, Mitsuyama K, Fujiyama Y (2005) Suppression of inflammatory cytokines secretion by granulocyte/monocytes adsorptive apheresis in active ulcerative colitis. Ther Apher Dial 2:123–127

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    Yoko Yokoyama, Ken Fukunaga, Yoshihiro Fukuda, Katsuyuki Tozawa, Koji Kamikozuru, Kunio Ohnishi, Takeshi Kusaka, Tadashi Kosaka, Nobuyuki Hida, Yoshio Ohda & Takayuki Matsumoto

  2. Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    Hiroto Miwa

Authors
  1. Yoko Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ken Fukunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshihiro Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katsuyuki Tozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Koji Kamikozuru
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kunio Ohnishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takeshi Kusaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tadashi Kosaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nobuyuki Hida
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yoshio Ohda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hiroto Miwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Takayuki Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ken Fukunaga.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yokoyama, Y., Fukunaga, K., Fukuda, Y. et al. Demonstration of Low-Regulatory CD25High+CD4+ and High-Pro-inflammatory CD28−CD4+ T-Cell Subsets in Patients with Ulcerative Colitis: Modified by Selective Granulocyte and Monocyte Adsorption Apheresis. Dig Dis Sci 52, 2725–2731 (2007). https://doi.org/10.1007/s10620-006-9560-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9560-z

Keywords

Search

Navigation