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CD34-expressing human thymocyte precursors proliferate in response to
interleukin-7 but have lost myeloid differentiation potential
C Schmitt, S Ktorza, S Sarun, C Blanc, R De Jong and P Debre
Laboratoire d'Immunologie cellulaire et Tissulaire, CNRS URA 625, CHU
Pitie-Salpetriere, Paris, France.
CD34 is a marker for pluripotent stem cells also present on lineage-
committed hematopoietic progenitors from bone marrow and a subpopulation of
immature thymocytes. To characterize these early immature thymocytes, we
have studied 24 pediatric thymus samples for CD34/7 expression. Three
subpopulations could be defined from these T- cell receptor (TcR-) immature
thymocytes: CD34+7++ (12.0 +/- 5.8), CD34- 7++ (12.6 +/- 8.6), and CD34-7+
(71.5 +/- 17.0%). CD7++ represents upregulation of this antigen and is
expressed by cells of a blast-like morphology. Three-color flow cytometric
analysis of these three subsets suggests the following ordered
differentiation sequence: CD34+7++1-4-8- 45RA+-->CD34+7++1+ 4+8-45RA+/-
-->CD34-7++1+4+8-+45RO+-->CD34- 7+1++4+8+45RO+. Early immature
thymocyte cell division is essential in the thymus to generate a large
number of precursors before the initiation of the selection process. We
observed that both CD2 as well CD28 activation pathways were inefficient to
serve as costimulant with phorbol ester 12-O-tetradecanoyl phorbol
13-acetate or interleukin-2 (IL-2) to induce the proliferation of the three
CD34/7 subsets isolated by cell sorting. However, whereas IL-1, IL-2, IL-3,
IL-4, granulocyte colony-stimulating factor, and granulocyte-macrophage
colony- stimulating factor were ineffective, IL-7 was a potent cytokine,
alone or in synergy with stem cell factor (SCF) to induce immature
thymocyte proliferation. The proliferation induced by IL-7 or IL-7 + SCF is
restricted to the CD34+ cells and, after 4 or 8 days of culture with IL- 7,
some CD34+7++ acquire the expression of CD4 and/or CD8, but remain
CD3/TcR-. We also tested the myeloid differentiation capacity of these CD34
immature thymocytes. Using two different approaches, myeloid colony
formation in methylcellulose and limiting dilution analysis in the presence
of myeloid growth factors, we were unable to detect myeloid differentiation
capacity from CD34+ early thymocytes, whereas CD34+7+ from bone marrow
contained about 10% of the clonogenic cells present in the CD34+7-
fraction. Together, these data support the concept that thymic CD34+7++
represents the earliest thymic subset of fully committed T-lineage cells,
capable of proliferating specifically to IL-7.
Volume 82,
Issue 12,
pp. 3675-3685,
12/15/1993
Copyright © 1993 by The American Society of Hematology
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