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 Blood, 15 August 2008, Vol. 112, No. 4, pp. 1515-1521.
Prepublished online as a Blood First Edition Paper on April 14, 2008; DOI 10.1182/blood-2007-11-125542.

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TRANSPLANTATION

Extracorporeal photopheresis reverses experimental graft-versus-host disease through regulatory T cells

Erin Gatza1, Clare E. Rogers1, Shawn G. Clouthier1, Kathleen P. Lowler1, Isao Tawara1, Chen Liu2, Pavan Reddy3, and James L. M. Ferrara1

1 Department of Pediatrics, University of Michigan Cancer Center, Ann Arbor; 2 Department of Pathology, University of Florida College of Medicine, Gainesville; and 3 Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor

Extracorporeal photopheresis (ECP), a technique that exposes isolated white blood cells to photoactivatable 8-methoxypsoralen and ultraviolet A radiation, is used clinically to treat cutaneous T-cell lymphoma and immune-mediated diseases such as graft-versus-host disease (GVHD). ECP is thought to control these diseases in part through direct induction of lymphocyte apoptosis, but its effects on the immune system beyond apoptosis remain poorly characterized. We have developed a novel method for incorporating ECP treatment into well-established and clinically relevant murine models of GVHD to examine its effects during an ongoing immune response. We demonstrate that the transfer of cells treated with ECP reverses established GVHD by increasing donor regulatory T cells and indirectly reducing the number of donor effector lymphocytes that themselves had never been exposed to psoralen and ultraviolet A radiation.


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