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Graft-Versus-Host Disease

Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease: positive correlation with response to photopheresis

Bone Marrow Transplantation volume 30, pages 509–515 (2002)Cite this article

Abstract

Chronic graft-versus-host disease (cGVHD) is a multiorgan disorder with skin manifestations resembling scleroderma. Since photopheresis, a treatment that induces an anticlonotypic immune response, has proven to be effective in both cutaneous T cell lymphomas with circulating clonal T cells and in cGVHD, we have searched for circulating clonal T cell populations in patients with cGVHD, and determined whether T cell clonality in the blood is associated with therapeutic response. We screened blood samples from 27 patients after HLA-matched allogeneic bone marrow transplantation (allo-BMT), 10 without cGVHD and 17 with extensive cGVHD, for clonal T cell receptor γ (TCRγ) gene rearrangements using fluorescent-based polymerase chain reaction (PCR) and automated high-resolution capillary electrophoresis. Amplified populations of clonal T cells with unique TCRγ gene rearrangements were found in six of 10 (60%) allo-BMT patients without cGVHD and 13 of 17 (76.5%) allo-BMT patients with cGVHD (P = 0.41), as compared to none of 10 (0%) healthy controls. Twelve patients with cGVHD were treated by photopheresis, and the presence of amplified populations of clonal T cells was found to be associated with a cutaneous response to photopheresis, as eight of eight (100%) clone-positive vs none of four (0%) clone-negative patients experienced a clinically significant cutaneous response to treatment (P = 0.001). Our findings suggest that patients with cGVHD that have detectable expanded clonal T cell populations in their peripheral blood, may be more likely to respond to treatment by photopheresis.

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References

  1. Ferrara JL, Deeg HJ . Graft-versus-host disease New Engl J Med 1991 324: 667 674

    Article  CAS  PubMed  Google Scholar 

  2. Vogelsang GB . Graft-versus-host disease: implications from basic immunology for prophylaxis and treatment Cancer Treat Res 1997 77: 87 97

    Article  CAS  PubMed  Google Scholar 

  3. Atkinson K . Chronic graft-versus-host disease Bone Marrow Transplant 1990 5: 69 82

    CAS  PubMed  Google Scholar 

  4. Sullivan KM, Witherspoon RP, Storb R et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease Blood 1998 72: 555 561

    Google Scholar 

  5. Sullivan KM, Witherspoon RP, Storb R et al. Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation Blood 1998 72: 546 554

    Google Scholar 

  6. Rook AH, Suchin KR, Kao DM et al. Photopheresis: clinical applications and mechanism of action J Invest Dermatol Symp Proc 1999 4: 85 90

    Article  CAS  Google Scholar 

  7. Rook AH, Freundlich B, Jegasothy BV et al. Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial (see comments) Arch Dermatol 1992 128: 337 346

    Article  CAS  PubMed  Google Scholar 

  8. Greinix HT, Volc-Platzer B, Rabitsch W et al. Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease Blood 1998 92: 3098 3104

    CAS  PubMed  Google Scholar 

  9. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host syndrome in man Am J Med 1980 69: 204 217

    Article  CAS  PubMed  Google Scholar 

  10. Kneba M, Bolz I, Linke B et al. Characterization of clone-specific rearrangement T-cell receptor gamma-chain genes in lymphomas and leukemias by the polymerase chain reaction and DNA sequencing Blood 1994 84: 574 581

    CAS  PubMed  Google Scholar 

  11. Luo V, Lessin SR, Wilson RB et al. Detection of clonal T-cell receptor gamma gene rearrangements using fluorescent-based PCR and automated high-resolution capillary electrophoresis Mol Diag 2001 6: 169 179

    CAS  Google Scholar 

  12. Olive C . T cell receptor usage in autoimmune disease Immunol Cell Biol 1995 73: 297 307

    Article  CAS  PubMed  Google Scholar 

  13. Vandevyver C, Mertens N, van den Elsen P et al. Clonal expansion of myelin basic protein-reactive T cells in patients with multiple sclerosis: restricted T cell receptor V gene rearrangements and CDR3 sequence Eur J Immunol 1995 25: 958 968

    Article  CAS  PubMed  Google Scholar 

  14. DerSimonian H, Sugita M, Glass DN et al. Clonal Vα12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients J Exp Med 1993 177: 1623 1631

    Article  CAS  PubMed  Google Scholar 

  15. Celis L, Vandevyver C, Geusens P et al. Clonal expansion of mycobacterial heat-shock protein-reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients Arthritis Rheum 1997 40: 510 519

    Article  CAS  PubMed  Google Scholar 

  16. Hingorani R, Choi IH, Akolkar P et al. Clonal predominance of T cell receptors within the CD8+ CD45RO+ subset in normal human subjects J Immunol 1993 151: 5762 5769

    CAS  PubMed  Google Scholar 

  17. Posnett DN, Sinha R, Kabak S, Russo C . Clonal populations of T cells in normal elderly humans: the T cell equivalent to ‘benign monoclonal gammapathy’ [Published erratum appears in J Exp Med 1994; 179: 1077] J Exp Med 1994 179: 609 618

    Article  CAS  PubMed  Google Scholar 

  18. Gorochov G, Debre P, Leblond V et al. Oligoclonal expansion of CD8+ CD57+ T cells with restricted T-cell receptor beta chain variability after bone marrow transplantation Blood 1994 83: 587 595

    CAS  PubMed  Google Scholar 

  19. Masuko K, Kato S, Hagihara M et al. Stable clonal expansion of T cells induced by bone marrow transplantation Blood 1996 87: 789 799

    CAS  PubMed  Google Scholar 

  20. Roux E, Helg C, Dumont-Girard F et al. Analysis of T-cell repopulation after allogeneic bone marrow transplantation: significant differences between recipients of T-cell depleted and unmanipulated grafts Blood 1996 87: 3984 3992

    CAS  PubMed  Google Scholar 

  21. Dumont-Girard F, Roux E, van Lier RA et al. Reconstitution of the T-cell compartment after bone marrow transplantation: restoration of the repertoire by thymic emigrants Blood 1998 92: 4464 4471

    CAS  PubMed  Google Scholar 

  22. Verfuerth S, Peggs K, Vyas P et al. Longitudinal monitoring of immune reconstitution by CDR3 size spectratyping after T-cell-depleted allogeneic bone marrow transplant and the effect of donor lymphocyte infusions on T-cell repertoire Blood 2000 95: 3990 3995

    CAS  PubMed  Google Scholar 

  23. Dietrich PY, Caignard A, Lim A et al. In vivo T-cell clonal amplification at time of acute graft-versus-host disease Blood 1994 84: 2815 2820

    CAS  PubMed  Google Scholar 

  24. Edelson R, Berger C, Gasparro F et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results New Engl J Med 1987 316: 297 303

    Article  CAS  PubMed  Google Scholar 

  25. Heald P, Rook A, Perez M et al. Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy (see comments) J Am Acad Dermatol 1992 27: 427 433

    Article  CAS  PubMed  Google Scholar 

  26. Gottlieb SL, Wolfe JT, Fox FE et al. Treatment of cutaneous T-cell lymphoma with extracorporeal photopheresis monotherapy and in combination with recombinant interferon alfa: a 10-year experience at a single institution J Am Acad Dermatol 1996 35: 946 957

    Article  CAS  PubMed  Google Scholar 

  27. Zic JA, Stricklin GP, Greer JP et al. Long-term follow-up of patients with cutaneous T-cell lymphoma treated with extracorporeal photochemotherapy J Am Acad Dermatol 1996 35: 935 945

    Article  CAS  PubMed  Google Scholar 

  28. Duvic M, Hester JP, Lemak NA . Photopheresis therapy for cutaneous T-cell lymphoma (see comments) J Am Acad Dermatol 1996 35: 573 579

    Article  CAS  PubMed  Google Scholar 

  29. Berger CL, Perez M, Laroche L, Edelson R . Inhibition of autoimmune disease in a murine model of systemic lupus erythematosus induced by exposure to syngeneic photoinactivated lymphocytes J Invest Dermatol 1990 94: 52 57

    Article  CAS  PubMed  Google Scholar 

  30. Girardi M, Herreid P, Tigelaar RE . Specific suppression of lupus-like graft-versus-host disease using extracorporeal photochemical attenuation of effector lymphocytes J Invest Dermatol 1995 104: 177 182

    Article  CAS  PubMed  Google Scholar 

  31. Perez MI, Edelson RL, John L et al. Inhibition of antiskin allograft immunity induced by infusions with photoinactivated effector T lymphocytes (PET cells) Yale J Biol Med 1989 62: 595 609

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Parkman R . Chronic graft-versus-host disease Curr Opin Hematol 1998 5: 22 25

    Article  CAS  PubMed  Google Scholar 

  33. Aractingi S, Chosidow O . Cutaneous graft-versus-host disease Arch Dermatol 1998 134: 602 612

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank K Duffy, B Denardo, P Bromley and WH Macey for help in collecting clinical samples. This work was supported in part by a grant from the National Institutes of Health CA 10815, and by a grant from the Leukemia and Lymphoma Society.

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Authors and Affiliations

  1. Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA

    LE French, M Shapiro, KS McGinnis, DJ Margolis & AH Rook

  2. Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    DGB Leonard

  3. Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    D Porter

  4. Department of Medicine, Tufts-New England Medical Center, Boston, MA, USA

    T Alcindor & F Foss

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French, L., Alcindor, T., Shapiro, M. et al. Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease: positive correlation with response to photopheresis. Bone Marrow Transplant 30, 509–515 (2002). https://doi.org/10.1038/sj.bmt.1703705

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