Abstract
The combination of 8-methoxypsoralen (8-MOP) and long wave ultraviolet radiation (UV-A) has immunomodulatory effects and might abolish both graft-vs-host and host-vs-graft reactions after allogeneic hematopoietic stem cell transplantation. In the present study, we have confirmed the sensitivity of T lymphocytes to 8-MOP treatment plus UV-A exposure as evidenced by the abrogation of the alloreactivity in mixed lymphocyte cultures as well as the inhibition of the response to phytohemagglutinin A. However, the clonogenic capacity of the bone marrow hematopoietic progenitors was inhibited with UV-A doses lower than the doses needed to inhibit T-lymphocytes alloreactivity. Moreover, long-term bone marrow cultures showed that 8-MOP plus UV-A treatment had detrimental effects on the more immature bone marrow stem cells. These data were confirmed when murine bone marrow graft was treated with 8-MOP, exposed to UV-A, then transplanted into semiallogeneic recipient mice. The treated cells could not maintain their clonogenic capacity in vivo resulting in death of all animals. Taken together, these data show that ex vivo 8-MOP plus UV-A treatment of the marrow graft cannot be used to prevent post-bone marrow transplantation alloreactivity.
Similar content being viewed by others
References
Socie G, Stone JV, Wingard JR, Weisdorf D, Henslee-Downey PJ, Bredeson C, Cahn JY, Passweg JR, Rowlings PA, Schouten HC, Kolb HJ, Klein JP (1999) Long-term survival and late deaths after allogeneic bone marrow transplantation. Late effects working committee of the international bone marrow transplant registry. N Engl J Med 341:14–21
Sodani P, Gaziev D, Polchi P, Erer B, Giardini C, Angelucci E, Baronciani D, Andreani M, Manna M, Nesci S, Lucarelli B, Clift RA, Lucarelli G (2004) New approach for bone marrow transplantation in patients with class 3 thalassemia aged younger than 17 years. Blood 104:1201–1203
Rao K, Amrolia PJ, Jones A, Cale CM, Naik P, King D, Davies GE, Gaspar HB, Veys PA (2005) Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen. Blood 105:879–885
Devetten MP, Vose JM (2004) Graft-versus-host disease: how to translate new insights into new therapeutic strategies. Biol Blood Marrow Transplant 10:815–825
Martin PJ, Hansen JA, Buckner CD, Sanders JE, Deeg HJ, Stewart P, Appelbaum FR, Reginald C, Fefer A, Witherspoon RP, Kennedy MS, Sulivan KM, Flounoy N, Storb R, Thomas ED (1985) Effects of in vitro depletion of T-cells in HLA identical allogeneic marrow grafts. Blood 66:664–672
Maraninchi D, Blaise D, Rio B, Leblond V, Dreyfus F, Gluclman E, Guyotat, Pico JL, Mi-chalet M, Ifrah N (1987) Impact of T-cell depletion on outcome of allogeneic bone marrow transplantation for standard-risk Ieukemias. Lancet 2:175–178
Marmont AM, Horowitz MM, Gale RP, Sobocinski K, Ash RC, van Bekkum DW, Champlin RE, Dicke KA, Goldman JM, Good RA (1991) T-cell depletion of HLA-identical transplants in leukemia. Blood 78:2120–2130
Keever CA, Small TN, Flomenberg N, Heller G, Pekle K, Black P, Pecora A, Gillio A, Kernan NA, O'Reilly RJ (1989) Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts. Blood 73:1340–1350
Soiffer RJ, Bosserman L, Murray C, Cochran K, Daley J, Ritz J (1990) Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation. Blood 75:2076–2084
Haddad E, Landais P, Friedrich W, Gerritsen B, Cavazzana-Calvo M, Morgan G, Bertrand Y, Fasth A, Porata F, Cant A, Espanol T, Muller S, Veys P, Vossen J, Fischer A (1998) Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients. Blood 91:3646–3653
Lewin SR, Heller G, Zhang L, Rodrigues E, Skulsky E, Marcel R, van den Brink M, Trudy N, Kernan NC, O'Reilly R, Ho DD, Young JW (2002) Direct evidence for new T-cell generation by patients after either T-cell-depleted or unmodified allogeneic hematopoietic stem cell transplantations. Blood 100:2235–2242
Tiberghien P, Herve P (1992) Perspectives in marrow graft T-cell depletion in allogeneic matched related bone marrow transplantation. Transf Sci 13:443–454
Schots R, Van Riet I, Ben Othman T, Trullemans F, De Waele M, Van Camp B (2001) The impact of partial T cell depletion on overall transplant-related toxicity, graft function and survival after HLA-identical allogeneic bone marrow transplantation in standard risk adult patients with leukemia. Bone Marrow Transplant 28:917–922
Keever-Taylor CA, Bredeson C, Loberiza FR, Casper JT, Lawton C, Rizzo D, Burns WH, Margolis DA, Vesole DH, Horowitz M, Zhang MJ, Juckett M, Drobyski WR (2001) Analysis of risk factors for the development of GVHD after T cell-depleted allogeneic BMT: effect of HLA disparity, ABO incompatibility, and method of T-cell depletion. Biol Blood Marrow Transplant 7:620–630
Deeg HJ (1992) Modification of allo-interactions and marrow transplantation by ultra-violet light. Semin Hematol 29:95–101
Lindahl-Keissling K, Safwenberg L (1971) Inability of UV-irradiated lymphocyte to stimulate allogeneic cells in mixed lymphocyte culture. Int Arch Allergy 1:670–678
Hudson JC, Lawer M, Pamphilon DH (1994) Ultraviolet irradiation for the prevention of graft versus host disease and graft rejection. Bone Marrow Transplant 14:511
Oluwole SF, Engelstod K, James T (1993) Prevention of graft versus host disease and bone marrow rejection: kinetics of induction of tolerance by UVB modulation of accessory cells and T-cells in the bone marrow inoculum. Blood 81:1658
Gowing H, Braakman E, Hagenbeek A, Lawler M, McCann SR, Pamphilon DH, Marten AC (1998) Influence of ultraviolet-B irradiation on engraftment, graft-versus-host-disease and graft-versus-leukemia effect in a rat model for allogeneic bone marrow transplantation. Bone Marrow Transplant 21:801–807
Greenfeld JI, Chabot JA, Oluwole SF, Hardy MA (1996) The mechanism of UVB prevention of graft versus host disease. J Surg Res 60:137–141
Deeg JH, Bazar L, Sigaroudinia M, Cottler-Fox M (1989) Ultraviolet B light inactivates bone marrow T-lymphocytes but spares hematopoietic precursor cells. Blood 73:369–371
Noizat Pirenne F, Greenfeld JI, Hardy MA, Oluwole SF, De Franchimont P (1996) UVB irradiation of human marrow: potential for donor specific tolerance. J Surg Res 61:267–274
Wolnicka-Glubisz A, Rijnkels JM, Sarna T, Beijersbergen van Henegouwen GM (2002) Apoptosis in leukocytes induced by UVA in the presence of 8-methoxypsoralen, chlorpromazine or 4,6,4′-trimethylangelicin. J Photochem Photobiol 68:65–72
Horio T, Okamoto H (1982) The mechanisms of inhibitory effects of 8-methoxypsoralen and long-wave ultra-violet light on experimental contact sensitization. J Invest Dermatol 78:402–405
Kripke NL, Morison WL, Parrish JA (1983) Systemic suppression of contact hyper sensitization in mice by psoralen plus UV-A radiation (PUVA). J Invest Dermatol 8:97–102
Morison WL, Parrish JA, Bloch KJ, Krugler JI (1981) In vitro effects of PUVA on lymphocyte function. Br J Dermatol 104:405–413
Moscicki RA, Morison WL, Parrish JA, Bloch KJ, Calvin RB (1982) Reduction of the functions of circulating helper–inducer T-cells identified by monoclonal antibodies in psoriatic patients treated with long-term psoralen ultraviolet-A radiation (PUVA). J Invest Dermatol 79:205–208
Dallamico R, Rossetti F, Zulian F, Montini G, Andreetta B, Messina C, Baradi E, Montesco MC, Dini G, Locatelii F, Argiolu F, Zacchello G (1997) Photopheresis in patients with drug-resistant chronic graft-versus-host-disease. Br J Haematol 97:848–854
Greinix HT, Volc-Platzer B, Kalhs P, Fisher G, Rosenmayr A, Keil F, Honigsmann H, Knobler RM (2000) Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study. Blood 96:2426–2431
Greinix HT, Volc-Platzer B, Knobler RM (2000) Extracorporeal photochemotherapy in the treatment of severe graft-versus-host disease. Leuk Lymphoma 36:425–434
Salvaneschi L, Perotti C, Zecca M, Bernuzzi S, Viarengo G, Giorgiani G, Del Fante C, Bergamaschi P, Maccario R, Pession A, Locatelli F (2001) Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood. Transfusion 41:1299–1305
Messina C, Locatelli F, Lanino E, Uderzo C, Zacchello G, Cesaro S, Pillon M, Perotti C, Del Fante C, Faraci M, Rivabella L, Calore E, De Stefano P, Zecca M, Giorgiani G, Brugiolo A, Balduzzi A, Dini G, Zanesco L, Dall'Amico R (2003) Extracorporeal photochemotherapy for paediatric patients with graft-versus-host disease after haematopoietic stem cell transplantation. Br J Haematol 122:118–127
Ullrich SE (1991) Photo-inactivation of T-cell function with psoralen and UV-A radiation suppresses the induction of experimental murine graft versus-host disease across major histocompatibility barriers. J Invest Dermatol 6:303–308
Burgess AW, Wilson HA, Metcalf D (1977) Stimulation by human placental conditioned medium of hemopoietic colony formation by human marrow cells. Blood 49:573–583
Garther S, Kaplan HS (1980) Long-term culture of human bone marrow cells. Proc Natl Acad Sci U S A 77:4756–4759
Jiang Z, Adams GB, Hanash AM, Scadden DT, Levy RB (2002) The contribution of cytotoxic and noncytotoxic function by donor T-cells that support engraftment after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 8:588–596
Raziuddin A, Longo DL, Mason L, Ortaldo JR, Benett M, Murphy WJ (1998) Differential effects of the rejection of bone marrow allografts by the depletion of activating versus inhibiting Ly-49 natural killer cell subsets. J Immunol 160:87–94
Raziuddin A, Bennett M, Winkeler-Pickett R, Ortaldo JR, Longo DL, Murphy WJ (2000) Synergistic effects of in vivo depletion of Ly-49A and Ly-49G2 natural killer cell subsets in the rejection of H2(b) bone marrow cell allografts. Blood 95:3840–3844
Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL (2002) CD4(+)CD25(+) immunoregulatory T Cells: new therapeutics for graft-versus-host disease. J Exp Med 196:401–406
Cohen J, Salomon B (2005) Therapeutic potential of CD4(+) CD25(+) regulatory T cells in allogeneic transplantation. Cytotherapy 7:166–170
Gowing H, Lawer M, Hagenbeek A, McCann SR, Pamphilpn DH, Hudson J, Weelden HV, Braakman E, Martens CM (1996) Effect of ultraviolet-B light on lymphocyte activity at doses at which normal bone marrow stem cells are preserved. Blood 87:1635–1643
Kraemer K, Levis WR, Caso JC, Tarone RE (1981) Inhibition of the mixed Leukocyte reaction by 8-methoxypsoralen and long-wave ultraviolet radiation. J Invest Dermatol 7:235–239
Edelson R, Jacobs D, Brin M, Khochevar I (1977) Lymphocyte sensitivity to 8-methoxypsoralen and ultra-violet A. Clin Res 25:281 A (abstr)
Truitt RL, Johnson BD, Hanke C, Talib S, Hearst JE (1999) Photochemical treatment with S-59 psoralen and ultraviolet A light to control the fate of naive or primed T lymphocytes in vivo after allogeneic marrow transplantation. J Immunol 163:5145–5156
Berger CL, Canter C, Welscg J (1985) Comparison of synthetic psoralen derivatives and 8-MOP in the inhibition of lymphatic proliferation. Ann N Y Acad Sci 446:80–90
Spielberg H, June CH, Blair OC, Nystrom-Rosander C, Cereb N, Deeg HJ (1991) UV irradiation of lymphocyte triggers an increase in intracellular Ca2+ mobilization. Evidence for UV and nifedipine sensitive Ca2+ channels. Exp Hematol 19:742–748
Schacter B, Lederman MM, Levine MJ, Elmer JJ (1983) Ultra-violet radiation inhibits human natural killer activity and lymphocyte proliferation. J Immunol 130:2484–2487
Amici LA, Gasparro FP (1995) 5-Methoxypsoralen photoadduct formation: conversion of monoadducts to crosslinks. Photodermatol Photoimmunol Photomed 11:135–139
Bevilacqua PM, Edelson RL, Gasparro FP (1991) High performance liquid chromatography analysis of 8-methoxy-psoralen monoadducts and cross-links in lymphocytes and keratinocytes. J Invest Dermatol 97:151–155
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mabed, M., Coffe, C., Racadot, E. et al. Differential sensitivity of T lymphocytes and hematopoietic precursor cells to photochemotherapy with 8-methoxypsoralen and ultraviolet A light. Ann Hematol 85, 17–24 (2006). https://doi.org/10.1007/s00277-005-0009-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-005-0009-9