Amotosalen-treated donor T cells have polyclonal antigen-specific long-term function without graft-versus-host disease after allogeneic bone marrow transplantation

Biol Blood Marrow Transplant. 2005 Mar;11(3):169-80. doi: 10.1016/j.bbmt.2004.12.332.


We have previously shown that amotosalen HCl (S-59 psoralen)-treated donor splenocytes, which have limited proliferative capacity in vitro, can protect major histocompatibility complex-mismatched bone marrow transplant (BMT) recipients from lethal murine cytomegalovirus infection without causing graft-versus-host disease. In this study, we further investigated the effects of amotosalen-treated donor T cells on immune reconstitution after allogeneic BMT. We were surprised to find that amotosalen-treated donor T cells persisted long-term in vivo, comprising 6% to 10% on average of the T-cell compartment of transplant recipients at 4 months after transplantation. Donor T cells derived from amotosalen-treated splenocytes were predominantly polyclonal CD44 hi/int CD8 + memory T cells and were functionally active, synthesizing interferon gamma in response to stimulation with murine cytomegalovirus antigen. Amotosalen-treated donor T cells, reisolated from BMT recipients' spleens >/=4 months after transplantation, proliferated in vitro, thus indicating repair of amotosalen-mediated DNA cross-links. Compared with infusion of untreated donor splenocytes, amotosalen-treated cells enhanced thymopoiesis by bone marrow-derived stem cells in BMT recipients. However, amotosalen treatment abrogated the thymopoietic activity of lymphoid progenitor cells among the donor splenocytes. Thus, infusion of amotosalen-treated donor T cells produced rapid immune reconstitution after major histocompatibility complex-mismatched BMT by transferring long-lived polyclonal memory T cells with antiviral activity and also by enhancing bone marrow-derived thymopoiesis. This is a novel approach to adoptive immunotherapy in allogeneic BMT.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / methods*
  • CD8 Antigens
  • Cell Proliferation
  • Furocoumarins / pharmacology
  • Furocoumarins / therapeutic use
  • Graft vs Host Disease / prevention & control*
  • Hyaluronan Receptors
  • Immune System / drug effects
  • Immune System / physiology
  • Immunologic Memory
  • Lymphopoiesis
  • Mice
  • Mice, Inbred Strains
  • Regeneration / drug effects
  • T-Cell Antigen Receptor Specificity*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Thymus Gland / cytology
  • Thymus Gland / physiology
  • Transplantation, Homologous


  • CD8 Antigens
  • Furocoumarins
  • Hyaluronan Receptors
  • amotosalen