Influence of TGF-beta on murine thymocyte development in fetal thymus organ culture.
TGF-beta is a multifunctional growth regulator that can either inhibit or stimulate the growth and differentiation of lymphocytes. For several cell types the effect of TGF-beta was found to correlate with the differentiation stage of the cells. We have studied the influence of TGF-beta on the differentiation of murine thymocytes by evaluating the effect of TGF-beta on the generation of thymocyte subpopulations in fetal thymus organ culture. TGF-beta inhibited the growth and differentiation of CD4-CD8- double-negative thymocytes. In the CD4-CD8- double-negative cell population, most cells remained CD44+CD25-, with CD44+CD25+ and CD44-CD25- subpopulations dramatically decreased in cell numbers. The accumulation of cells with a phenotype characteristic of cells in early stage of differentiation suggests a block at very early transition steps. These observations were confirmed in experiments with precursor cells from fetal liver transferred to 2-deoxyguanosine-treated alymphoid thymic lobes, inasmuch as addition of TGF-beta caused a complete inhibition of T cell development. Differentiation into CD4+CD8+ double-positive thymocytes and CD4+ single-positive thymocytes was impaired because these cell numbers were greatly reduced. In contrast, the CD8+ single-positive subpopulation retained normal cell numbers. This CD8+ population had characteristics of a mature subset as the cells expressed CD8 beta and high levels of TCR-alpha beta and CD3. This TCR-alpha beta + cell population was not actively dividing, suggesting that these cells arise de novo by differentiation.
Plum
J
J
Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, University Hospital, Belgium.
De Smedt
M
M
Leclercq
G
G
Vandekerckhove
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000096:biosynthesis; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D004247:DNA / Q000032:analysis; D005314:Embryonic and Fetal Development / Q000276:immunology; D005434:Flow Cytometry; D018960:Hyaluronan Receptors; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing; D016212:Transforming Growth Factor beta; D004247:DNA