Abstract • 167
Interleukin (IL)-2 has successfully been used for induction of a Graft versus Leukemia effect (GvL) after allogeneic bone marrow transplantation (BMT). However, severe graft versus host disease (GvHD) might limit the therapeutic width of IL-2 (Slavin et al., Blood 87: 2195 - 2204, 1996). Studies in patients after BMT reveal that a decreased ex vivo production of IL-10 and an increased production of IFN-γ are associated with occurrence of GvHD. Preliminary results on detection of cytoplasmatic cytokine expression in PMA/ionomycine treated PBMC show an increase of IFY-γ production at onset of GvHD, suggesting that T-1 activation might be involved in the pathogenesis of human GvHD. Since recent observations in mice demonstrate that T-2 polarized donor lymphocytes could induce GvL without GvHD (Uharek et al., Bone Marrow Transpl. 21 Suppl 1, p68), an in vitro model on the regulation of IL-2 induced human T-cell activation was established. The results of these analyses indicate that a combined application of IL-2 and IL-10 inhibits T-1, but not T-2 activation. In addition, IL-2 induced IFN-γ production was almost completely suppressed by IL-10, while release of an important mediator of T-cell cytotoxicity, sFasL, was only partially reduced. These data might help develop new strategies for improved immunotherapy after BMT.
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Körholz, D., Kim, Y., Finkensieper, T. et al. Differential regulatory function of T-cell subsets on graft versus host and graft versus leukemia reactions after stem cell transplantation: Development of strategies for selective induction of a GvL reaction. Pediatr Res 45 (Suppl 5), 770 (1999). https://doi.org/10.1203/00006450-199905010-00197
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DOI: https://doi.org/10.1203/00006450-199905010-00197