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Early posttransplant infusion of cryopreserved bone marrow T cells following induction of mixed chimerism could induce chimeric conversion in MHC‐mismatched nonmyeloablative Bone Marrow Transplantation.
Author(s) -
Cho Seok Goo,
Park Hyun Sil,
Park Min Jung,
Min So Youn,
Park Mi Kyung,
Kim Ho Youn
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.530
Subject(s) - chimera (genetics) , splenocyte , bone marrow , spleen , medicine , immunology , donor lymphocyte infusion , cd8 , transplantation , cryopreservation , mixed lymphocyte reaction , t cell , antigen , immune system , graft versus host disease , chemistry , biology , embryo , gene , microbiology and biotechnology , biochemistry
In clinical practice, donor lymphocyte infusion (DLI) has been often used to augment GVL effect in patients with posttransplantation leukemic relapse. Recently, intentional induction of allogeneic mixed chimerism has been expected to have important potentials not only in waning susceptibility to GVHD, but also to provide immunologic platform for subsequent DLI. In this study we evaluated the potential of cryopreserved bone marrow T cells (Thy1.2+) for the chimeric conversion in early post‐transplant period of allogeneic mixed chimerism which were obtained from T‐cell depletion step of BM graft. Chimeric conversions of mixed chimera using CD8+ splenocytes (1x10 6 ) and unmaupulated spleen cell (10x10 6 ), and cryopreserved BM T cells were successfully achieved without serious GVHD. However DLI using CD4+ splenocytes showed serious DLI‐induced GVHD and sustained mixed chimeric state. When the same dose of T cells isolated from BM and spleen were administered into mixed chimera mice, BM‐T group showed complete chimeric conversion with transient GVHD and no pathologic changes compared to spleen‐T group. This study suggested that BM T cells are more potent to induce chimeric conversion with small dose of DLI than that spleen cells. Cryopreserved BM T cells obtained during TCD procedure might be effectively used to consolidate donor dominant chimerism in clinical practice without concerns of GVHD.