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Suppress a Stimulatory Graft-versus-Host Disease with a Lupus-Like Syndrome1
Departments of
*
Medicine and
Pathology, Division of Rheumatology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
Regulatory T cells generated ex vivo from conventional mouse T cells have been used to prevent and alter the course of a stimulatory graft-vs-host disease with a lupus-like syndrome. DBA/2 mouse T cells induce this syndrome when injected into (DBA/2 x C57BL/6) F1 mice. Stimulating DBA/2 T cells with irradiated C57BL/6 in the presence of IL-2 and TGF-
induced both CD4+ and CD8+ cells to develop potent suppressive activity and enhanced their survival. The IL-2 and TGF--treated T cells lost their ability to induce graft-vs-host disease and, instead, prevented other parental T cells from inducing lymphoid hyperplasia, B cell activation, and an immune complex glomerulonephritis. Moreover, a single transfer of TGF--conditioned T cells to animals that had already developed anti-dsDNA Abs decreased the titer, suppressed proteinuria, and doubled survival. This study raises the possibility that autologous regulatory T cells generated ex vivo have the potential to be used as an adoptive immunotherapy to induce allograft tolerance and to control autoimmunity.
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