Plenary paper P-glycoprotein targeting: a unique strategy to selectively eliminate immunoreactive T cells

T lymphocytes have been found to harbor P-glycoprotein (Pgp) and to demonstrate modulation of its ion channel transporter function according to the state of activa-tion of T lymphocytes. We hypothesized that cytotoxic chemicals that are ex-truded by Pgp could be used to specifi-cally eliminate immunoreactive T-cell populations. In this study, we evaluated the capacity of 4,5-dibromorhodamine methyl ester (TH9402), a photosensitizer structurally similar to rhodamine, a dye transported by Pgp, and which becomes highly cytotoxic on activation with visible light to selectively deplete alloreactive T lymphocytes. Stimulation of T cells with mitogens or allogeneic major histocom-patibility complex–mismatched cells re-sulted in the preferential retention of the TH9402 rhodamine-derivative in activated T cells, both CD4 and CD8. Photody-namic cell therapy of TH9402-exposed T cells led to the selective elimination of immunoreactive T-cell populations. In ad-dition, this treatment preserved resting T cells and their capacity to respond to third-party cells. Inhibition of Pgp en-hanced cellular trapping of the dye in nonactivated T cells and resulted in their depletion after exposure to light. Target-ing of Pgp-deficient cells may therefore represent an appealing strategy for the prevention and treatment of graft-versus-host disease and other alloimmune or autoimmune disorders. (Blood. 2002;100