We have investigated the ability of a heterogeneous thymic stromal cell (HTSC) culture system to promote in vitro differentiation of CD3-4-8- thymocytes. Culture of purified murine CD3-4-8- thymocytes on HTSC for 1 d resulted in the appearance of CD4+8+ cells, which did not occur when the sorted cells were maintained in medium alone. It is remarkable that when the culture period was extended to 2 d, CD3-4-8- progenitors differentiated further to CD4+8- and CD4-8+ cells, which also expressed high levels of TCR-CD3. This rapid differentiation on stroma in vitro appears to outpace parallel development in vivo. The differentiation potential of a subset of CD3-4-8- thymocytes that express high levels of a marker of normal and neoplastic thymic progenitors, the 1C11 antigen, was examined next. 1C11hiCD3-4-8- cells also gave rise to CD4-8+ and CD4+8+ populations after 1 d of culture on HTSC. Extending the culture period to 2 d resulted in a significant percentage of CD3-expressing cells that were CD4+8+, CD4+8- and CD4-8+ cells. These results suggest that in the in vitro HTSC culture system, various subsets of immature thymocytes can differentiate into all the mature phenotypes of cells normally found in the adult mouse thymus. This may provide a novel and rapid assay for thymic progenitors.
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http://dx.doi.org/10.1084/jem.176.2.543 | DOI Listing |
Anticancer Res
November 2004
Institute of Molecular Immunology, Medinet, Tamagawadai, Setagaya-ku, Tokyo 158-0096 and 2Seta Clinic, 4-20-18 Seta, Setagayaku, Tokyo 158-0095, Japan.
Background: We previously reported that the Q5 gene product (Q5 antigen) was expressed on the surface of various tumor cells derived from H-2k (Qa-2-) mice. The Q5 antigen has tumor-protective antigenicity in the syngeneic mice.
Materials And Methods: Transcripts of the Qa region genes were analyzed by the RT-PCR method.
Blood
November 2002
Department of Biological Structure, School of Medicine, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195-7420, USA.
Here we demonstrate that keratinocyte growth factor (KGF) and FGFR2IIIb signaling can affect development and function of thymic epithelium (TE) and that alphabeta-lineage thymocytes contribute to intrathymic levels of KGF. Thymocyte expression of KGF is developmentally regulated, being undetectable in CD3-4-8- thymocytes and expressed at highest levels by mature CD4 or CD8 thymocytes. Exposure of thymocyte-depleted fetal thymic lobes to KGF resulted in reduced thymic epithelial expression of class II major histocompatibility complex (MHC), invariant chain (Ii), and cathepsin L (CatL) molecules involved in thymocyte-positive selection and also stimulated expression of the cytokines interleukin 6 (IL-6) and thymic stromal-derived lymphopoietin (TSLP), while having little effect on IL-7 or stem cell factor expression.
View Article and Find Full Text PDFBMC Immunol
September 2002
Department of Genetics, University of Georgia, Athens, Georgia 30602 USA.
Background: The function of the thymic microenvironment is to promote thymocyte maturation, in part via regulation of thymocyte proliferation and cell death. Defects in fetal thymic epithelial cell (TEC) development and function, and therefore in the formation of a functional microenvironment, can be caused either directly by TEC differentiation defects or indirectly by defective thymocyte maturation. In this paper we studied fetal thymocyte proliferation during the early transition from the CD3-4-8- (triple negative, TN) to CD4+8+ (double positive, DP) stages.
View Article and Find Full Text PDFOntogenez
September 2002
Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe sh. 24, Moscow, 115478 Russia.
It was shown using complement-dependent cytolysis and monoclonal antibodies against CD4, CD8, and NK1.1 antigens that the cortisone-resistant CD3+4-8-NK1.1(-)-thymocytes spontaneously secreted a chemotactic transmitter inducing the release and directed migration of bone marrow cells.
View Article and Find Full Text PDFDev Immunol
March 2001
Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, Canada.
Thymocyte differentiation involves several processes that occur in different anatomic sites within the thymus. Therefore, thymocytes must have the ability to respond to signals received from stromal cells and adopt either adhesive or motile behavior. We will discuss our data indicating human thymocytes use alpha4beta1 integrin, alpha5beta1 integrin and RHAMM to mediate these activities.
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