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In vitro T lymphopoiesis of human and rhesus CD34+ progenitor cells
M Rosenzweig, DF Marks, H Zhu, D Hempel, KG Mansfield, PK Sehgal, S Kalams, DT Scadden and RP Johnson
Division of Immunology, New England Regional Primate Research Center,
Harvard Medical School, Southborough, MA 01772, USA.
Differentiation of hematopoietic progenitor cells into T lymphocytes
generally occurs in the unique environment of the thymus, a feature that
has hindered efforts to model this process in the laboratory. We now report
that thymic stromal cultures from rhesus macaques can support T-cell
differentiation of human or rhesus CD34+ progenitor cells. Culture of
rhesus or human CD34+ bone marrow-derived cells depleted of CD34+
lymphocytes on rhesus thymic stromal monolayers yielded CD3+CD4+CD8+,
CD3+CD4+CD8-, and CD3+CD4-CD8+ cells after 10 to 14 days. In addition to
classical T lymphocytes, a discrete population of CD3+CD8loCD16+CD56+ cells
was detected after 14 days in cultures inoculated with rhesus CD34+ cells.
CD3+ T cells arising from these cultures were not derived from
contaminating T cells present in the CD34+ cells used to inoculate thymic
stromal monolayers or from the thymic monolayers, as shown by labeling of
cells with the lipophilic membrane dye PKH26. Expression of the recombinase
activation gene RAG- 2, which is selectively expressed in developing
lymphocytes, was detectable in thymic cultures inoculated with CD34+ cells
but not in CD34+ cells before thymic culture or in thymic stromal
monolayers alone. Reverse transcriptase-polymerase chain reaction analysis
of T cells derived from thymic stromal cultures of rhesus and human CD34+
cells showed a polyclonal T-cell receptor repertoire. T-cell progeny
derived from rhesus CD34+ cells cultured on thymic stroma supported
vigorous simian immunodeficiency virus replication in the absence of
exogenous mitogenic stimuli. Rhesus thymic stromal cultures provide a
convenient means to analyze T-cell differentiation in vitro and may be
useful as a model of hematopoietic stem cell therapy for diseases of T
cells, including acquired immunodeficiency syndrome.
Volume 87,
Issue 10,
pp. 4040-4048,
05/15/1996
Copyright © 1996 by The American Society of Hematology
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