Korean J Intern Med.  2009 Sep;24(3):252-262. 10.3904/kjim.2009.24.3.252.

Bone Marrow T Cells are Superior to Splenic T Cells to Induce Chimeric Conversion After Non-Myeloablative Bone Marrow Transplantation

Affiliations
  • 1Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea College of Medicine, Seoul, Korea.
  • 2Catholic Hematopoietic Stem Cell Transplantation Center, The Catholic University of Korea College of Medicine, Seoul, Korea. chosg@catholic.ac.kr
  • 3Department of Radiation Oncology, The Catholic University of Korea College of Medicine, Seoul, Korea.

Abstract

BACKGROUND/AIMS
The bone marrow functions not only as the primary B-lymphocyte-producing organ but also as a secondary lymphoid organ for CD4 and CD8 cell responses and a site of preferential homing and persistence for memory T cells. Bone marrow T (BM-T) cells are distinguished from peripheral blood T cells by surface phenotype, cytokine secretion profile, and immune functions. In this study, we evaluated the alloreactive potential of donor lymphocyte infusion (DLI) using BM-T cells in mixed chimerism compared to that using spleen T (SP-T) cells. METHODS: Cells were prepared using established procedures. BM-T cells were obtained as a by-product of T-cell depletion in BM grafting and then cryopreserved for subsequent DLI. We performed DLI using BM-T cells in allogeneic mixed chimera mice on post-BMT day 21. RESULTS: When the same dose of T cells, 5-10x10(5) (Thy1.2+), fractionated from BM and spleen were administered into mixed chimeras, the BM-T group showed complete chimeric conversion, with self-limited graft-versus-host disease (GVHD) and no pathological changes. However, the SP-T group showed persistent mixed chimerism, with pathological signs of GVHD in the liver and intestine. CONCLUSIONS: Our results suggest that DLI using BM-T cells, even in small numbers, is more potent at inducing chimeric conversion in mixed chimerism than DLI using SP-T cells. Further study is needed to determine whether cryopreserved BM-T cells are an effective cell source for DLI to consolidate donor-dominant chimerism in clinical practice without concerns about GVHD.

Keyword

Chimerism, mixed; Infusion, donor lymphocyte; T-cells, bone marrow

MeSH Terms

Animals
Bone Marrow Cells/*physiology
*Bone Marrow Transplantation
Female
Graft vs Host Disease/prevention & control
*Lymphocyte Transfusion
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Spleen/*cytology
T-Lymphocytes/*physiology
Tissue Donors
Transplantation Chimera
Transplantation, Homologous
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