Photochemical treatment with S-59 psoralen and ultraviolet A light to control the fate of naive or primed T lymphocytes in vivo after allogeneic bonemarrow transplantation

Donor leukocyte infusions after allogeneic bone marrow transplantation can provide a curative graft-vs-leukemia (GVL) effect, but there is a significa nt risk of graft-vs-host (GVH) disease. A simple and effective method for c ontrolling the fate of naive or primed T-lymphocytes in vivo without elimin ating 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 G VH potential of naive and primed donor T cells in vivo. S-59 rapidly interc alates 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 PC T regimens, treated T cells still expressed activation markers (CD25 and CD 69) 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 a fter PCT, but short term lytic activity of primed CTL was not affected. In a murine model of MHC-mismatched bone marrow transplantation, the addition bf PCT-treated T cells to T-depleted bone marrow facilitated donor engraftm ent and complete chimerism without causing acute or chronic graft-vs-host d isease. Allospecific GVL reactivity was reduced but not eliminated after PC T treatment. In an MHC-matched model using host-presensitized donor T cells , PCT significantly reduced GVH-associated mortality without eliminating GV L reactivity, Thus, PCT ex vivo offers a simple, rapid, and inexpensive met hod by which to control the fate of naive and primed T cells in vivo.