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Post-Transplant Events

Development of T cell-mediated immunity after autologous stem cell transplantation: prolonged impairment of antigen-stimulated production of γ-interferon

Bone Marrow Transplantation volume 40, pages 261–266 (2007)Cite this article

Abstract

The conditioning regimens for autologous SCT (auto-SCT) lead to impairment of the immune system and concomitant increase in susceptibility to infections. We studied the recovery of cellular immunity by in vitro analysis of T-cell proliferation and cytokine production profiles during the first 15 months after auto-SCT in patients with multiple myeloma and non-Hodgkin's lymphoma. PBMC were collected at 6, 9 and 15 months after transplantation and stimulated with a combination of CD2 and CD28 monoclonal antibodies, with PHA or with tetanus toxoid as recall antigen. A multiplex enzyme linked immunoassay was used to determine levels of Th1 cytokines IL-2, IFN-γ and tumour-necrosis factor-α (TNF-α), Th2 cytokines IL-4, IL-5 and IL-13, the regulatory cytokine IL-10 and the proinflammatory cytokines IL-1α, IL-1β, IL-6 and the chemokine IL-8. T-cell proliferation progressively increased from 6 to 15 months after auto-SCT. Overall, cytokine production increased after auto-SCT. Production of Th2 cytokines IL-5 and IL-13 was superior to production of Th1 cytokines IFN-γ and TNF-α. We hypothesize that prolonged impairment of IFN-γ production might contribute to the relatively high incidence of viral infections after auto-SCT.

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References

  1. Barlogie B, Shaughnessy J, Tricot G, Jacobson J, Zangari M, Anaissie E et al. Treatment of multiple myeloma. Blood 2004; 103: 20–32.

    Article  CAS  Google Scholar 

  2. Van Imhoff GW, Van der Holt B, MacKenzie MA, Van 't Veer MB, Wijermans PW, Ossenkoppele GJ et al. Dutch-Belgian Hemato-Oncology Cooperative Group. Impact of three courses of intensified CHOP prior to high-dose sequential therapy followed by autologous stem-cell transplantation as first-line treatment in poor-risk, aggressive non-Hodgkin's lymphoma: comparative analysis of Dutch-Belgian Hemato-Oncology Cooperative Group Studies 27 and 40. J Clin Oncol 2005; 23: 3793–3801.

    Article  CAS  Google Scholar 

  3. Larsson K, Bjorkstrand B, Ljungman P . Faster engraftment but no reduction in infectious complications after peripheral blood stem cell transplantation compared to autologous bone marrow transplantation. Support Care Cancer 1998; 6: 378–383.

    Article  CAS  Google Scholar 

  4. Molldrem JJ . Vaccinating transplant recipients. Nat Med 2005; 11: 1162–1163.

    Article  CAS  Google Scholar 

  5. Porrata LF, Litzow MR, Markovic SN . Immune reconstitution after autologous hematopoietic stem cell transplantation. Mayo Clin Proc 2001; 76: 407–412.

    Article  CAS  Google Scholar 

  6. Guillaume T, Rubinstein DB, Symann M . Immune reconstitution after autologous hematopoietic stem cell transplantation. Blood 1998; 92: 1471–1490.

    CAS  PubMed  Google Scholar 

  7. Lossos IS, Breuer R, Or R, Strauss N, Elishoov H, Naparstek E et al. Bacterial pneumonia in recipients of bone marrow transplantation. A five-year prospective study. Transplantation 1995; 60: 672–678.

    Article  CAS  Google Scholar 

  8. Frere P, Pereira M, Fillet G, Beguin Y . Infections after CD34-selected or unmanipulated autologous hematopoietic stem cell transplantation. Eur J Haematol 2006; 76: 102–108.

    Article  Google Scholar 

  9. Van der Velden AMT, Claessen AM, van Velzen-Blad H, Biesma DH, Rijkers GT . Development of functional haemophilus influenzae type b antibodies after vaccination. Haematologica 2005; 90: 1582–1584.

    PubMed  Google Scholar 

  10. Vance E, George S, Guinan EC, Wheeler C, Antin JH, Ambrosino DM et al. Comparison of multiple immunization schedules for haemophilus influenzae type b-conjugate and tetanus toxoid vaccines following bone marrow transplantation. Bone Marrow Transplant 1998; 22: 735–741.

    Article  CAS  Google Scholar 

  11. Nachbaur D, Kropshoger G, Heitger A, Latzer K, Glassl H, Ludescher C et al. Phenotypic and functional lymphocyte recovery after CD34+-enriched versus non-T cell-depleted autologous peripheral blood stem cell transplantation. J Hematother Stem Cell Res 2000; 9: 727–736.

    Article  CAS  Google Scholar 

  12. De Jager W, te Velthuis H, Prakken BJ, Kuis W, Rijkers GT . Simultaneous detection of 15 human cytokines in a single sample of stimulated peripheral blood mononuclear cells. Clin Diagn Lab Immunol 2003; 10: 133–139.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Borish LC, Steinke JW . Cytokines and chemokines. J Allergy Clin Immunol 2003; 111: S460–S475.

    Article  CAS  Google Scholar 

  14. Street NE, Mosmann TR . Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J 1991; 5: 171–177.

    Article  CAS  Google Scholar 

  15. De Vries E, de Bruin-Versteeg S, Comans-Bitter WM, de Groot R, Hop WCJ, Boerma GJM et al. Longitudinal survey of lymphocyte subpopulations in the first year of life. Pediatr Res 2000; 47: 528–537.

    Article  CAS  Google Scholar 

  16. Avigan D, Wu Z, Joyce R, Elias A, Richardson P, McDermott D et al. Immune reconstitution following high-dose chemotherapy with stem cell rescue in patients with advanced breast cancer. Bone Marrow Transplant 2000; 26: 169–176.

    Article  CAS  Google Scholar 

  17. Akpek G, Lenz G, Lee SM, Sanchorawala V, Wright DG, Colarusso T et al. Immunologic recovery after autologous blood stem cell transplantation in patients with AL-amyloidosis. Bone Marrow Transplant 2001; 28: 1105–1109.

    Article  CAS  Google Scholar 

  18. Te Boekhorst PWA, Lamers CHJ, Schipperus MR, Hintzen RQ, Van der Holt B, Cornelissen JJ et al. T-lymphocyte reconstitution following rigorously T-cell-depleted versus unmodified autologous stem cell transplants. Bone Marrow Transplant 2006; 37: 763–772.

    Article  CAS  Google Scholar 

  19. Guillaume T, Sekhavat M, Rubinstein DB, Hamdan O, Leblanc P, Symann ML . Defective cytokine production following autologous stem cell transplantation for solid tumors and hematologic malignancies regardless of bone marrow or peripheral origin and lack of evidence for a role for interleukin-10 in delayed immune reconstitution. Cancer Res 1994; 54: 3800–3807.

    CAS  PubMed  Google Scholar 

  20. Singh RK, Varney L, Ino K, Vose JM, Bierman PJ, Talmadge JE . Immune dysfunction despite high levels of immunoregulatory cytokine gene expression in autologous peripheral blood stem cell transplanted non-Hodgkin's lymphoma patients. Exp Hematol 2000; 28: 499–507.

    Article  CAS  Google Scholar 

  21. Steinke JW, Borish L . Cytokines and chemokines. J Allergy Clin Immunol 2006; 117: S441–S445.

    Article  CAS  Google Scholar 

  22. Finkelman FD, Katona IM, Mosmann TR, Coffman RL . IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol 1988; 140: 1022–1027.

    CAS  PubMed  Google Scholar 

  23. Schlenke P, Sheikhzadeh S, Weber K, Wagner T, Kirchner H . Immune reconstitution and production of intracellular cytokines in T lymphocyte populations following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2001; 28: 251–257.

    Article  CAS  Google Scholar 

  24. Zeng D, Dejbaksh-Jones S, Srober S . Granulocyte colony-stimulating factor reduces the capacity of blood mononuclear cells to induce graft-versus-host disease: impact on blood progenitor cell transplantation. Blood 1997; 90: 453–456.

    CAS  PubMed  Google Scholar 

  25. Pan L, Delmonte J, Jalonen C, Ferrara J . Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine propduction and reduces severity of experimental graft-versus-host disease. Blood 1995; 86: 4422–4429.

    CAS  PubMed  Google Scholar 

  26. Sloand EM, Kim S, Maciejewski JP, Van Rhee F, Chaudhuri A, Barrett J et al. Pharmacological doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo. Blood 2000; 95: 2269–2274.

    CAS  PubMed  Google Scholar 

  27. Han CS, Miller W, Haake R, Weisdorf D . Varicella zoster infection after bone marrow transplantation: incidence, risk factors and complications. Bone Marrow Transplant 1994; 13: 277–283.

    CAS  PubMed  Google Scholar 

  28. Lee SH, Aggarwal BB, Rinderknecht E, Assisi F, Chiu H . The synergistic anti-proliferative effect of gamma-interferon and human lymphotoxin. J Immunol 1984; 133: 1083–1086.

    CAS  PubMed  Google Scholar 

  29. Warren MK, Vogel SN . Opposing effects of glucocorticoids on interferon-gamma-induced murine macrophage Fc receptor and Ia antigen expression. J Immunol 1985; 134: 2462–2469.

    CAS  PubMed  Google Scholar 

  30. Ljungman P, Engelhard D, de la Cámara R, Einsele H, Locasciulli A, Martino R et al. Vaccination of stem cell transplant recipients: recommendations of the Infectious Diseases Working Party of the EBMT. Bone Marrow Transplant 2005; 35: 737–746.

    Article  CAS  Google Scholar 

  31. Sullivan KM, Dykewicz CA, Longworth DL, Boeckh M, Baden LR, Rubin R et al. Preventing opportunistic infections after hematopoietic stem cell transplantation: the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond. Hematology (Am Soc Hematol Educ Program) 2001; 1: 392–421.

    Article  Google Scholar 

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Acknowledgements

We thank Dr MR de Groot, haematologist at Medical Spectrum Twente in Enschede and Dr MHH Kramer, haematologist at Meander Medical Centre in Amersfoort, for recruiting patients in this study. The Dutch Cancer Society financially supported this work.

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Authors and Affiliations

  1. Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands

    A M T van der Velden & D H Biesma

  2. Department of Haematology, VU Medical Centre, Amsterdam, The Netherlands

    A M T van der Velden

  3. Department of Medical Microbiology & Immunology, St Antonius Hospital, Nieuwegein, The Netherlands

    A M E Claessen, H van Velzen-Blad & G T Rijkers

  4. Department of Immunology, Laboratory of Paediatric Immunology, University Children's Hospital ‘Het Wilhelmina Kinderziekenhuis’/University Medical Centre Utrecht, Utrecht, The Netherlands

    G T Rijkers

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  1. A M T van der Velden
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  2. A M E Claessen
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  3. H van Velzen-Blad
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  4. D H Biesma
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  5. G T Rijkers
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Correspondence to A M T van der Velden.

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van der Velden, A., Claessen, A., van Velzen-Blad, H. et al. Development of T cell-mediated immunity after autologous stem cell transplantation: prolonged impairment of antigen-stimulated production of γ-interferon. Bone Marrow Transplant 40, 261–266 (2007). https://doi.org/10.1038/sj.bmt.1705706

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