Allogeneic donor T cells in bone marrow transplantation (BMT) can contribute to @entity2132 (GVL) effects but can also cause @entity2132 ( @entity2132 ). A successful method for the ex vivo treatment of donor T cells to limit their @entity2132 potential while retaining GVL activity would have broad clinical applications for @entity1 undergoing allogeneic hematopoietic cell transplantation for @entity5 . We hypothesized that donor lymphocyte infusions treated with @entity3118 , an immunosuppressive @entity2353 analog, would have reduced @entity2132 potential in a fully major histocompatibility complex-mismatched C57BL/6 --> B10.BR @entity19 BMT model. Recipients of @entity3118 -treated donor lymphocyte infusions (F-DLI) had significantly reduced @entity2132 mortality, reduced histopathologic evidence of @entity2132 , and lower inflammatory serum cytokine levels than recipients of untreated DLI. Combined comparisons of @entity2132 incidence and donor-derived hematopoietic chimerism indicated that F-DLI had a therapeutic index superior to that of untreated DLI. Furthermore, adoptive immunotherapy of @entity981 using F-DLI in the C57BL/6 --> B10.BR model demonstrated a broad therapeutic index with markedly reduced @entity2132 activity and preservation of GVL activity compared with untreated allogeneic T cells. @entity3118 exposure markedly reduced the @entity404 + @entity1759 (low)-naive donor T-cell population within 48 hours of transplantation and altered the relative representation of cytokine-producing @entity404 + T cells, consistent with T-helper type 2 polarization. However, proliferation of @entity3118 -treated T cells in allogeneic recipient spleens was equivalent to that of untreated T cells. The results suggest that @entity3118 reduces the @entity2132 potential of donor lymphocytes through effects on a @entity404 + @entity1759 (low) T-cell population, with less effect on alloreactive T cells and @entity404 + @entity1759 (high) memory T cells that are able to mediate GVL effects. Thus, F-DLI represents a novel method of immune modulation that may be useful to enhance immune reconstitution among allograft recipients with reduced risk of @entity2132 while retaining beneficial GVL effects.

Ex vivo XXXX exposure inhibits graft-versus-host activity of allogeneic T cells while preserving graft-versus-leukemia effects.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity2353 :: ('CHEBI:33838', 'Chemical') :: ['nucleoside'] @entity981 :: ('MESH:D054198', 'Disease') :: ['lymphoblastic lymphoma'] @entity404 :: ('920', 'Gene') :: ['CD4'] @entity5 :: ('MESH:D009369', 'Disease') :: ['malignant diseases'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity1759 :: ('960', 'Gene') :: ['CD44'] @entity3118 :: ('MESH:C024352', 'Chemical') :: ['Fludarabine', 'fludarabine'] @entity2132 :: ('MESH:D006086', 'Disease') :: ['detrimental graft-versus-host disease', 'beneficial graft-versus-leukemia', 'GVHD']
@entity3118 :: (MESH:C024352,Chemical) :: ['fludarabine']
