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Lymphocyte reconstitution after allogeneic bone marrow transplantation in a previously thymectomized patient—no evidence of extrathymic T-cell maturation

Bone Marrow Transplantation volume 40, pages 705–706 (2007)Cite this article

The thymus is the main organ of T-cell maturation in humans. However, it regresses at puberty, whereas T-cell rearrangement continues even in the elderly,1 and there is a hypothesis that the function of the thymus may partially be replaced by other tissues including the intestinal epithelium. Indeed, intraepithelial lymphocytes located in the small intestinal mucosa were found to express recombination activating genes RAG 1, RAG 2 and pre-T α-chain, which are all required for T-cell receptor (TCR) rearrangement.2, 3, 4 Although these findings strongly suggest the presence of extrathymic T-cell maturation (ETCM), no direct evidence of this phenomenon has been provided so far.

To search for clinical evidence of ETCM, we studied immune reconstitution in a 27-year-old male patient who was initially diagnosed with thymoma. We performed a thymectomy, followed by irradiation of the mediastinum. One year later, he developed ALL, was treated with chemotherapy, achieved complete remission and was referred for bone marrow transplant from an HLA-identical unrelated donor (URD-BMT). The conditioning regimen was myeloablative and consisted of busulfan, cyclophosphamide and anti-thymocyte globulin. Ex vivo T-cell depletion was not performed. Prophylaxis of GvHD included cyclosporine and short-course methotrexate. Hematopoietic recovery occurred on day +29. Full donor chimerism was achieved on day +30 and remained stable with 20 months follow-up. The patient did not develop acute GvHD and experienced only transient symptoms of limited chronic GvHD. The only infectious complication was Varicella zoster, which appeared 10 months after transplantation and was successfully treated with acyclovir. The patient remains alive and disease free 20 months after URD-BMT.

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References

  1. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998; 396: 690–695.

    Article  CAS  PubMed  Google Scholar 

  2. Lundqvist C, Baranov V, Hammarstrom S, Athlin L, Hammarstrom ML . Intra-epithelial lymphocytes: evidence for regional specialization and extrathymic T cell maturation in the human gut epithelium. Int Immunol 1995; 7: 1473.

    Article  CAS  PubMed  Google Scholar 

  3. Lynch S, Kelleher D, McManus R, O'Farrelly C . RAG1 and RAG2 expression in human intestinal epithelium: evidence of extrathymic T cell differentiation. Eur J Immunol 1995; 25: 1143.

    Article  CAS  PubMed  Google Scholar 

  4. Bas A, Hammarstrom S, Hammarstrom M-L . Extrathymic TCR gene rearrangement in human small intestine: identification of new splice forms of recombination activating gene-1 mRNA with selective tissue expression. J Immunol 2003; 171: 3359–3371.

    Article  CAS  PubMed  Google Scholar 

  5. Patel DD, Gooding ME, Parrott RE, Curtis KM, Haynes BF, Buckley RH . Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Eng J Med 2000; 342: 1325.

    Article  CAS  Google Scholar 

  6. Mackall CL, Granger L, Sheard MA, Cepeda R, Gress RE . T cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived versus thymic independent progeny. Blood 1993; 82: 2585–2594.

    CAS  PubMed  Google Scholar 

  7. Hazenberg MD, Otto SA, de Pauw ES, Roelofs H, Fibbe WE, Hamann D et al. T cell receptor excision circle and T cell dynamics after allogeneic stem cell transplantation are related to clinical events. Blood 2002; 99: 3449–3452.

    Article  CAS  PubMed  Google Scholar 

  8. Heitger A, Greinix H, Mannhalter C, Mayerl D, Kern H, Eder J et al. Requirement of residual thymus to restore normal T cell subsets after human allogeneic bone marrow transplantation. Transplantation 2000; 69: 2366–2373.

    Article  CAS  PubMed  Google Scholar 

  9. Watanabe N, De Rosa SC, Cmelak A, Hoppe R, Herzenberg LA, Roederer M . Long-term depletion of naive T cells in patients treated for Hodgkin's disease. Blood 1997; 90: 3662–3672.

    CAS  PubMed  Google Scholar 

  10. Faint JM, Annels NE, Curnow SJ, Shields P, Pilling D, Hislop AD et al. Memory T cells constitute a subset of the human CD8+CD45RA+ pool with distinct phenotypic and migratory characteristics. J Immunol 2001; 167: 212–220.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Haematology and BMT, Silesian Medical University, Katowice, Poland

    S Giebel, J Dziaczkowska, J Wojnar, M Krawczyk-Kulis & J Holowiecki

  2. Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

    B Wysoczanska & A Lange

  3. Lower Silesian Center for Cellular Transplantation, Wroclaw, Poland

    A Lange

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  1. S Giebel
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  2. J Dziaczkowska
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Correspondence to S Giebel.

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Giebel, S., Dziaczkowska, J., Wysoczanska, B. et al. Lymphocyte reconstitution after allogeneic bone marrow transplantation in a previously thymectomized patient—no evidence of extrathymic T-cell maturation. Bone Marrow Transplant 40, 705–706 (2007). https://doi.org/10.1038/sj.bmt.1705794

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