Bone marrow T cells are superior to splenic T cells to induce chimeric conversion after non-myeloablative bone marrow transplantation.
OBJECTIVE
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.
Park
Hyun-Sil
HS
Rheumatism Research Center, Catholic Research Institutes of Medical Science, Seoul, Korea.
Cho
Seok-Goo
SG
Park
Min-Jung
MJ
Min
So-Youn
SY
Chang
Hong-Seok
HS
Kim
Hee-Je
HJ
Lee
Seok
S
Min
Chang-Ki
CK
Lee
Jong-Wook
JW
Min
Woo-Sung
WS
Kim
Chun-Choo
CC
Kim
Ho-Youn
HY
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology*; D013601:T-Lymphocytes / Q000502:physiology*; D014019:Tissue Donors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous