Clinical stem-cell sources contain CD8+CD3+ T-cell receptor-negative cells that facilitate bone marrow repopulation with hematopoietic stem cells.
Clinical observations in patients undergoing bone marrow transplantation implicate the involvement of CD8(+) cells in promoting the stem-cell engraftment process. These findings are supported by mouse transplant studies, which attributed the engraftment-facilitating function to subpopulations of murine CD8(+) cells, but the analogous cells in humans have not been identified. Here, we report that clinical stem-cell grafts contain a population of CD8alpha(+)CD3epsilon(+) T-cell receptor- negative cells with an engraftment facilitating function, named candidate facilitating cells (cFCs). Purified cFC augmented human hematopoiesis in NOD/SCID mice receiving suboptimal doses of human CD34(+) cells. In vitro, cFCs cocultured with CD34(+) cells increased hematopoietic colony formation, suggesting a direct effect on clonogenic precursors. These results provide evidence for the existence of rare human CD8(+)CD3(+)TCR(-) cells with engraftment facilitating properties, the adoptive transfer of which could improve the therapeutic outcome of stem-cell transplantation.
Bridenbaugh
Stephanie
S
Experimental Hematology, Department of Research, University Hospital Basel, Basel, Switzerland.
Kenins
Linda
L
Bouliong-Pillai
Emilie
E
Kalberer
Christian P
CP
Shklovskaya
Elena
E
Gratwohl
Alois
A
Wodnar-Filipowicz
Aleksandra
A
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell