Interleukin-4 protects double-negative and CD4 single-positive thymocytes from dexamethasone-induced apoptosis.

Glucocorticoid hormones (GCH) and anti-CD3 monoclonal antibodies (MoAbs) induce in mouse thymocytes and T-cell tumor lines an active process of cell death called apoptosis. Interleukins (IL), including IL-1 and IL-2, have been reported to inhibit such apoptosis. In this study we show that IL-4 also reduced the DNA fragmentation characteristic of dexamethasone (DEX)-induced apoptosis in thymocytes. This effect, studied in both time-course and dose-response experiments, was also detected at low IL-4 concentrations (1 U/mL) and against high DEX levels (10(-7) mol/L). The effect of IL-4 was blocked by an anti-IL-4 but not by an anti-IL-1 alpha MoAb, and was thus both specific and direct. Phenotypic analysis showed that IL-4 protects predominantly CD4-CD8- and CD4+CD8- cells. Our findings suggest that intrathymic T-cell development may be influenced by IL-4.

[1]  K. Rajewsky,et al.  Generation and analysis of interleukin-4 deficient mice. , 1991, Science.

[2]  I Nicoletti,et al.  A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. , 1991, Journal of immunological methods.

[3]  M. Collins,et al.  Regulation of apoptosis in interleukin‐3‐dependent hemopoietic cells by interleukin‐3 and calcium ionophores. , 1990, The EMBO journal.

[4]  M. Nieto,et al.  IL-2 protects against anti-CD3-induced cell death in human medullary thymocytes. , 1990, Journal of immunology.

[5]  M. Toribio,et al.  A role for interleukin 4 in the differentiation of mature T cell receptor gamma/delta + cells from human intrathymic T cell precursors , 1990, The Journal of experimental medicine.

[6]  T. Tadakuma,et al.  CD4+CD8+ thymocytes are susceptible to DNA fragmentation induced by phorbol ester, calcium ionophore and anti‐CD3 antibody , 1990, European journal of immunology.

[7]  S. Orrenius,et al.  Interleukin 1 inhibits T cell receptor-mediated apoptosis in immature thymocytes. , 1990, The Journal of biological chemistry.

[8]  M. Nieto,et al.  IL-2 protects T cell hybrids from the cytolytic effect of glucocorticoids. Synergistic effect of IL-2 and dexamethasone in the induction of high-affinity IL-2 receptors. , 1989, Journal of immunology.

[9]  M. Nieto,et al.  IL-2 protects T lymphocytes from glucocorticoid-induced DNA fragmentation and cell death. , 1989, Journal of immunology.

[10]  S. Orrenius,et al.  Calcium-dependent killing of immature thymocytes by stimulation via the CD3/T cell receptor complex. , 1989, Journal of immunology.

[11]  Beni M. Sahai,et al.  Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes , 1989, Nature.

[12]  R. Kingston,et al.  Developmental control of lymphokine gene expression in fetal thymocytes during T-cell ontogeny. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

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

[14]  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.

[15]  M. Brown,et al.  IL-4/B cell stimulatory factor 1 stimulates T cell growth by an IL-2-independent mechanism. , 1988, Journal of immunology.

[16]  J. Sprent,et al.  T Cell Selection in the Thymus , 1988, Immunological reviews.

[17]  J. Lowenthal,et al.  Up-regulation of interleukin 4 receptor expression on immature (Lyt-2-/L3T4-) thymocytes. , 1988, Journal of immunology.

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

[19]  P. Sideras,et al.  Recombinant interleukin 4/BSF‐1 promotes growth and differentiation of intrathymic T cell precursors from fetal mice in vitro. , 1987, The EMBO journal.

[20]  J. Cohen,et al.  Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. , 1984, Journal of immunology.

[21]  A. Wyllie Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation , 1980, Nature.

[22]  K. Burton A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. , 1956, The Biochemical journal.

[23]  P. Marrack,et al.  The T-cell repertoire for antigen and MHC. , 1988, Immunology today.

[24]  P. Sideras,et al.  Analysis by in situ hybridization of cells expressing mRNA for interleukin 4 in the developing thymus and in peripheral lymphocytes from mice. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Wyllie,et al.  Cell death: the significance of apoptosis. , 1980, International review of cytology.