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Identification of human T‐lymphoid progenitor cells in CD34 + CD38 low and CD34 + CD38 + subsets of human cord blood and bone marrow cells using NOD‐SCID fetal thymus organ cultures
Author(s) -
Robin Catherine,
BennaceurGriscelli Annelise,
Louache Fawzia,
Vainchenker William,
Coulombel Laure
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01266.x
Subject(s) - cd38 , cord blood , cd34 , bone marrow , progenitor cell , lymphopoiesis , haematopoiesis , biology , cd8 , stromal cell , myeloid , stem cell , immunology , microbiology and biotechnology , antigen , cancer research
In contrast to myeloid and B‐lymphoid differentiation, which take place in the marrow environment, development of T cells requires the presence of thymic stromal cells. We demonstrate in this study that human CD34 + , CD34 + CD38 + and CD34 + CD38 low cells from both cord blood and adult bone marrow reproducibly develop into CD4 + CD8 + T cells when introduced into NOD‐SCID embryonic thymuses and further cultured in organotypic cultures. Such human/mouse FTOC (fetal thymic organ culture) thus represents a reproducible and sensitive system to assess the T‐cell potential of human primitive progenitor cells. The frequency of T‐cell progenitors among cord‐blood‐derived CD34 + cells was estimated to be 1/500. Furthermore, the differentiation steps classically observed in human thymus were reproduced in NOD‐SCID FTOC initiated with cord blood and human marrow CD34 + cells: immature human CD4 low CD8 − sCD3 − TCRαβ – CD5 + CD1a + T cells were mixed with CD4 + CD8 + cells and more mature CD4 + CD8 − TCRαβ + cells. However, in FTOC initiated with bone marrow T progenitors, <10% double‐positive cells were observed, whereas this proportion increased to 50% when cord blood CD34 + cells were used, and most CD4 + cells were immature T cells. These differences may be explained by a lower frequency of T‐cell progenitors in adult samples, but may also suggest differences in the thymic signals required by bone marrow versus cord blood T progenitors. Finally, since cytokine‐stimulated CD34 + CD38 low cells retained their ability to generate T cells, these FTOC assays will be of value to monitor, when combined with other biological assays, the influence of different expansion protocols on the potential of human stem cells.