Development of fetal thymocytes in organ culture: effect of corticosteroids.

Corticosteroids affect the development of fetal foregut-derived organs in which epithelial-mesenchymal interactions are associated with the developmental process. The thymus is one such organ and is profoundly sensitive to corticosteroids when mature. In this study corticosterone (CS) effects on fetal thymocyte development were investigated using a fetal thymus organ culture system which allows the growth, differentiation, and function of developing thymocytes to be monitored in vitro. CS inhibited, but did not block growth of fetal thymocytes, although the appearance of mature thymocytes was inhibited, similar to previously reported effects of interleukin 2 (IL2). CS enhanced the proportion of Mac1+, Ia+ and FcR+ cells and maintained high levels of IL2 receptor (IL2R) positive immature cells. Functional cytotoxic cells were detected in CS-treated organ cultures which expressed a Thy 1-, CD8- phenotype, atypical for thymus derived killer cells. While this cytotoxicity may be stimulated by CS, it could simply be due to a relative depletion of the main pool of thymocytes. These cytotoxic cells may have a role in directing apoptotic mechanisms occurring during thymocyte development.

[1]  W. van Ewijk T-cell differentiation is influenced by thymic microenvironments. , 1991, Annual review of immunology.

[2]  W. Kuziel,et al.  Natural killer cells in the thymus. Studies in mice with severe combined immune deficiency. , 1990, Journal of immunology.

[3]  E. Jenkinson,et al.  T-cell differentiation in thymus organ cultures. , 1990, Seminars in immunology.

[4]  R. Schwartz Acquisition of immunologic self-tolerance , 1989, Cell.

[5]  M. Skinner,et al.  Development of thymocytes in organ culture: Migrant cells with natural killer cell characteristics , 1989, Immunology and cell biology.

[6]  H. von Boehmer,et al.  The thymus selects the useful, neglects the useless and destroys the harmful. , 1989, Immunology today.

[7]  Gwyn T. Williams,et al.  Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures , 1989, Nature.

[8]  S. Rosenberg,et al.  Lymphokine-Activated Killer Cells , 1989 .

[9]  J. Watson,et al.  Growth of fetal thymocytes in organ culture: effect of recombinant lymphokines on thymocyte maturation. , 1989, Growth factors.

[10]  D. Pardoll,et al.  Molecular and cellular events of T cell development. , 1989, Advances in immunology.

[11]  M. Caligiuri,et al.  Induction of natural killer effectors from human thymus with recombinant IL-2. , 1988, Journal of immunology.

[12]  Z. Ballas,et al.  Lymphokine-activated killer (LAK) cells. III. Characterization of LAK precursors and susceptible target cells within the murine thymus. , 1987, Journal of immunology.

[13]  J. Cohen,et al.  Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes. , 1987, Journal of immunology.

[14]  H. Ertl,et al.  Lymphokines induce specificity degradation in virus-induced cytolytic T-cell clones. , 1987, Cellular immunology.

[15]  J. Watson,et al.  Development of fetal thymocytes in organ cultures. Effect of interleukin 2 , 1987, The Journal of experimental medicine.

[16]  D. Ucker Cytotoxic T lymphocytes and glucocorticoids activate an endogenous suicide process in target cells , 1987, Nature.

[17]  M. Melis,et al.  The influence of dexamethasone treatment on the lymphoid and stromal composition of the mouse thymus: a flowcytometric and immunohistological analysis. , 1986, Cellular immunology.

[18]  I. Barr,et al.  Thymic sensitivity to sex hormones develops post-natally; an in vivo and an in vitro study. , 1984, Journal of Immunology.

[19]  Barry T. Smith,et al.  Concepts of epithelial‐mesenchymal interactions during development: Tooth and lung organogenesis , 1984, Journal of cellular biochemistry.

[20]  K. Shortman,et al.  The functional capacity of thymus subpopulations: limit-dilution analysis of all precursors of cytotoxic lymphocytes and of all T cells capable of proliferation in subpopulations separated by the use of peanut agglutinin. , 1982, Journal of immunology.

[21]  A. Tanswell,et al.  Influence of corticosteroids on glycogen content and steroid 11-reductase activity in lung and liver of the fetal and newborn rat. , 1982, Biology of the neonate.

[22]  T. Mandel,et al.  Differentiation of T Lymphocytes in Organ Cultures of Fetal Mouse Thymus: Analysis of Cells Using Monoclonal Antibodies and Flow Cytometry , 1981 .

[23]  I. Trowbridge,et al.  Effects of cytotoxic monoclonal antibody specific for T200 glycoprotein on functional lymphoid cell populations. , 1980, Cellular immunology.

[24]  L. Herzenberg,et al.  Xenogeneic Monoclonal Antibodies to Mouse Lymphoid Differentiation Antigens * , 1979, Immunological reviews.