Skip to main content

Advertisement

Log in

Skewed T-cell subsets and enhanced macrophages phagocytosis in the spleen of patients with immune thrombocytopenia failing glucocorticoids

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

T-cell abnormalities are considered important in the pathogenesis of immune thrombocytopenia (ITP). Th1 polarization of the immune response in peripheral blood mononuclear cells (PBMC) has been observed in ITP patients. However, whether the polarization of T-cell subsets exists in splenocytes remains unclear. In the present study, we detected T-cell subsets and macrophage phagocytosis capacity in the spleens of ten ITP patients failing first-line treatment. Compared with traumatic patients, ITP patients had similar percentages of Th1, Tc1, and T1 (Th1 + Tc1) cells, but lower percentages of Th2 and Tc2 cells, which did not, however, reach significant difference. ITP patients had significantly lower percentages of T2 (Th2 + Tc2) cells than the control group (P = 0.035). The ratios of Th1/Th2 and T1/T2 were significantly higher in ITP patients than the control group (P = 0.025 and 0.027, respectively). Splenic macrophages from ITP patients presented significant increase in phagocytic capacity (P < 0.001). The phagocytosis rate in splenic macrophages positively correlated with the ratio of Th1/Th2 (r = 0.767, P = 0.010), but negatively correlated with percentage of Th2 cells (r = −0.804, P = 0.005). The skewed T-cell subsets and enhanced macrophage phagocytosis in the spleen may be closely related to the disease onset and status of ITP.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Nugent D, McMillan R, Nichol JL, Slichter SJ. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol. 2009;146:585–96.

    Article  CAS  PubMed  Google Scholar 

  2. Cines DB, McKenzie SE, Siegel DL. Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2003;25:S52–6.

    Article  PubMed  Google Scholar 

  3. George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40.

    CAS  PubMed  Google Scholar 

  4. British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120:574–96.

    Article  Google Scholar 

  5. Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168–86.

    Article  CAS  PubMed  Google Scholar 

  6. Pizzuto J, Ambriz R. Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: Multicentric Trial of the Cooperative Latin American group on Hemostasis and Thrombosis. Blood. 1984;64:1179–83.

    CAS  PubMed  Google Scholar 

  7. Ben-Yehuda D, Gillis S, Eldor A. Clinical and therapeutic experience in 712 Israeli patients with idiopathic thrombocytopenic purpura. Israeli ITP Study Group. Acta Haematol. 1994;91:1–6.

    Article  CAS  PubMed  Google Scholar 

  8. Najean Y, Rain JD, Billotey C. The site of destruction of autologous 111In-labelled platelets and the efficiency of splenectomy in children and adults with idiopathic thrombocytopenic purpura: a study of 578 patients with 268 splenectomies. Br J Haematol. 1997;97:547–50.

    Article  CAS  PubMed  Google Scholar 

  9. Sarpatwari A, Provan D, Erquo S, Sobnack R, Tai FWD, Newland AC. Autologous 111In-labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry. Br J Haematol. 2010;151:477–87.

    Article  PubMed  Google Scholar 

  10. Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004;104:2623–34.

    Article  CAS  PubMed  Google Scholar 

  11. Kawana M, Ikeda Y. The role of autoreactive T-Cells in the pathogenesis of idiopathic thrombocytopenic purpura. Int J Hematol. 2005;81:106–12.

    Article  Google Scholar 

  12. Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC, et al. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood. 2004;103:2645–7.

    Article  CAS  PubMed  Google Scholar 

  13. Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, et al. High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;71:283–8.

    Article  CAS  PubMed  Google Scholar 

  14. Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica. 2005;90:914–23.

    CAS  PubMed  Google Scholar 

  15. Zhang J, Ma D, Zhu X, Qu X, Ji CY, Hou M. Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura. Haematologica. 2009;94:1326–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kuwana M, Okazaki Y, Kaburaki J, Kawakami Y, Ikeda Y. Spleen is a primary site for activation of platelet-reactive T and B cells in patients with immune thrombocytopenic purpura. J Immunol. 2002;168:3675–82.

    Article  CAS  PubMed  Google Scholar 

  17. Yan F, Li ZF, Zhang S, Yang JH, Li AM, Liu XG. Isolation and purification of macrophages from human spleen. Xi’an Jiaotong Daxue Xuebao. 2004;25:452–5.

    Google Scholar 

  18. Cosmi L, Annunziato F, Galli MIG, Maggi RME, Nagata K, Romagnani S. CRTH2 is the most reliable marker for the detection of circulating human type 2 Th and type 2 T cytotoxic cells in health and disease. Eur J Immunol. 2000;30:2972–9.

    Article  CAS  PubMed  Google Scholar 

  19. Kuwana M, Kaburaki J, Ikeda Y. Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody. J Clin Invest. 1998;102:1393–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kuwana M. Autoantibodies to platelets: roles in thrombocytopenia. Inflamm Regen. 2009;29:40–6.

    Article  CAS  Google Scholar 

  21. Olsson B, Andersson PO, Jernås M, Jacobsson S, Carlsson B, Carlsson LM, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9:1123–4.

    Article  CAS  PubMed  Google Scholar 

  22. Zhang F, Chu X, Wang L, Zhu Y, Li L, Ma D, et al. Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2006;76:427–31.

    Article  CAS  PubMed  Google Scholar 

  23. Sakakura M, Wada H, Tawara I, Nobori T, Sugiyama T, Sagawa N, et al. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura. Thromb Res. 2007;120:187–93.

    Article  CAS  PubMed  Google Scholar 

  24. Ling Y, Cao X, Yu Z, Ruan C. Circulating dendritic cells subsets and CD4+Foxp3+ regulatory T cells in adult patients with chronic ITP before and after treatment with high-dose dexamethasome. Eur J Haematol. 2007;79:310–6.

    Article  CAS  PubMed  Google Scholar 

  25. Liu B, Zhao H, Poon MC, Han Z, Gu D, Xu M, et al. Abnormality of CD4+CD25+ regulatory T cells in idiopathic thrombocytopenic purpura. Eur J Haematol. 2007;78:139–43.

    CAS  PubMed  Google Scholar 

  26. Lafaille JJ. The role of helper T cell subsets in autoimmune diseases. Cytokine Growth Factor Rev. 1998;9:139–51.

    Article  CAS  PubMed  Google Scholar 

  27. Kuwana M, Okazaki Y, Ikeda Y. Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost. 2009;7:322–9.

    Article  CAS  PubMed  Google Scholar 

  28. Panitsas FP, Mouzaki A. Effect of splenectomy on type-1/type-2 cytokine gene expression in a patient with adult idiopathic thrombocytopenic purpura (ITP). BMC Blood Disord. 2004;4:4.

    PubMed  PubMed Central  Google Scholar 

  29. Cuker A, Cines DB. Evidence-Based Mini-Review: Is Indium-Labeled Autologous Platelet Scanning Predictive of Response to Splenectomy in Patients With Chronic Immune Thrombocytopenia? Hematology Am Soc Hematol Educ Program. 2010:385–6.

  30. Stout RD, Bottomly K. Antigen-specific activation of effector macrophages by IFN-gamma producing (TH1) T cell clones. Failure of IL-4-producing (TH2) T cell clones to activate effector function in macrophages. J Immunol. 1989;142:760–5.

    CAS  PubMed  Google Scholar 

  31. Estaquier J, Ameisen JC. A role for T-helper type-1 and type-2 cytokines in the regulation of human monocyte apoptosis. Blood. 1997;90:1618–25.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Sichuan Provincial Bureau of Science and Technology (2008SZ0195).

Conflict of interest

All the authors declared that they had no interests which may be perceived as posing a conflict or bias.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bing Peng.

About this article

Cite this article

Chen, X., Chen, S., Li, C. et al. Skewed T-cell subsets and enhanced macrophages phagocytosis in the spleen of patients with immune thrombocytopenia failing glucocorticoids. Int J Hematol 94, 248–254 (2011). https://doi.org/10.1007/s12185-011-0908-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-011-0908-6

Keywords

Navigation