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Flow cytometric assessment of human T-cell differentiation in thymus and
bone marrow
LW Terstappen, S Huang and LJ Picker
Becton Dickinson Immunocytometry Systems, San Jose, CA 95131.
Using multidimensional flow cytometry we have defined and quantified the
human T-cell differentiation pathway, focusing on those events occurring
among the most immature thymocytes and putative bone marrow (BM)
T-precursors. Early thymocytes were found to express the CD34 antigen and
consisted of a mean 1.2% of cells within human pediatric (n = 9) and 2.0%
in fetal thymi (n = 4). All CD34+ thymocytes were atypical blast by
morphology, expressed intracytoplasmatic, but not cell surface, CD3, and
were cell surface CD2+, CD5+, CD7+, CD38+, CD45+, CD45RA+, CD49d+, and
LECAM-1(Leu8)high. CD34high thymocytes lacked surface expression of CD4 and
CD8, but as CD34 expression diminished there was a coordinate increase in
CD4 levels, followed by the appearance of CD8. The expression of CD1 and
CD10 also increased concomitant with the loss of CD34, whereas expression
of LECAM-1 diminished with CD34 downregulation. The differential expression
of these antigens on early thymocytes (as well as the number of thymocytes
displaying these patterns) was highly reproducible among the nine pediatric
and four fetal specimens examined, suggesting a precise, stereotyped
regulation of early differentiation events. Cell populations with antigen
expression patterns suggestive of pluripotent stem cell (CD34high, CD38-),
or non-T-lineage committed stem cells (CD34+, CD33+ or CD34+, CD19+) were
not identified in either fetal or pediatric thymi (sensitivity = 1/10(4)).
The presence of cells with the antigenic profile of the earliest CD34+
thymocytes was explored in human BM. Putative BM T-cell precursors with the
appropriate phenotype (CD34+, CD7+, CD5+, CD2+, LECAM-1high) were readily
identified in fetal specimens (constituting +/- 2% of the CD34+
population), but could not be reliably detected in adults. In contrast with
thymi, only 13% of these cells expressed cytoplasmatic CD3, suggesting the
presence of the immediate precursor of the putative prothymocyte
population. This was further supported by the detection of CD34bright,
CD7+, CD2-, CD5-, LECAM-1moderate cells in fetal specimens. Our results
document the flow of cell surface differentiation during T-lymphopoiesis
and suggest that T-lineage features are first acquired in the BM. The
ability to reproducibly identify and isolate T-cell precursor populations
of precisely defined maturational stage in marrow and thymus by
multiparameter flow cytometry will facilitate characterization of the
molecular events controlling T-lineage differentiation.
Volume 79,
Issue 3,
pp. 666-677,
02/01/1992
Copyright © 1992 by The American Society of Hematology
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