Photochemical treatment with S-59 psoralen and ultraviolet A light to control the fate of naive or primed T lymphocytes in vivo after allogeneic bone marrow transplantation. J Immunol 1999 Nov 01;163(9):5145-56
Date
10/21/1999Pubmed ID
10528221Scopus ID
2-s2.0-0032711448 (requires institutional sign-in at Scopus site) 48 CitationsAbstract
Donor leukocyte infusions after allogeneic bone marrow transplantation can provide a curative graft-vs-leukemia (GVL) effect, but there is a significant risk of graft-vs-host (GVH) disease. A simple and effective method for controlling the fate of naive or primed T-lymphocytes in vivo without eliminating their beneficial properties is needed. In this report, photochemical treatment (PCT) ex vivo with a synthetic psoralen (S-59) and UVA light was evaluated as a pharmacological approach to limiting the proliferation and GVH potential of naive and primed donor T cells in vivo. S-59 rapidly intercalates into and cross-links DNA on UVA illumination. The effects of PCT on T cells were found to be both S-59 and UVA dose dependent. With selected PCT regimens, treated T cells still expressed activation markers (CD25 and CD69) and secreted IL-2 on activation, but they showed limited proliferative capacity in vitro and in vivo. Clonal expansion of CTL in MLR was reduced after PCT, but short term lytic activity of primed CTL was not affected. In a murine model of MHC-mismatched bone marrow transplantation, the addition of PCT-treated T cells to T-depleted bone marrow facilitated donor engraftment and complete chimerism without causing acute or chronic graft-vs-host disease. Allospecific GVL reactivity was reduced but not eliminated after PCT treatment. In an MHC-matched model using host-presensitized donor T cells, PCT significantly reduced GVH-associated mortality without eliminating GVL reactivity. Thus, PCT ex vivo offers a simple, rapid, and inexpensive method by which to control the fate of naive and primed T cells in vivo.
Author List
Truitt RL, Johnson BD, Hanke C, Talib S, Hearst JEAuthor
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, CD
Antigens, Differentiation, T-Lymphocyte
Bone Marrow Transplantation
Cells, Cultured
Clonal Anergy
Cytokines
Cytotoxicity, Immunologic
Dose-Response Relationship, Immunologic
Ficusin
Furocoumarins
Graft vs Host Reaction
Lectins, C-Type
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Male
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
PUVA Therapy
Radiation Chimera
Radiation-Sensitizing Agents
Receptors, Interleukin-2
T-Lymphocytes
T-Lymphocytes, Cytotoxic
Time Factors
Transplantation, Homologous
