Are the IL-2 Receptors Expressed in the Murine Fetal Thymus Functional?

It is well established that the majority of murine fetal thymocytes (day 15 of gestation) express receptors for interleukin 2 (IL-2), but the functional significance of these IL-2 receptors (IL-2Rs) is not clear. In situ hybridization data show a developmentally regulated expression of IL-2 and IL-2R mRNA. IL-2 binding studies were performed on fetal thymocytes and the results show the presence of both high (kD ≅ 20 pM) and low (kD ≅ 10 nM) affinity IL-2Rs. These IL-2Rs are indeed functional: intact fetal thymic lobes (but not cell suspensions) cultured in IL-2 exhibited an in vitro proliferative response at 20 pM of IL-2, corresponding with the presence of a functional high-affinity IL-2R on fetal thymocytes. The IL-2-dependent growth was primarily observed in the IL-2R + thymic subset, which contains the CD3-/CD4-/CD8- precursor thymocytes. Furthermore, in vitro blocking of IL-2 in intact fetal thymic lobes resulted in a reduction in the cell yield, which predominantly affected the expansion of the immature CD3-/CD4-/CD8-thymocytes. Our findings strongly support the concept that the IL-2/IL-2R pathway is responsible for the proliferation of precursor cells within the fetal thymus.

[1]  J. Watson,et al.  Effect of IL-7 on the growth of fetal thymocytes in culture. , 1989, Journal of immunology.

[2]  C. Pénit,et al.  Cell proliferation and differentiation in the fetal and early postnatal mouse thymus. , 1989, Journal of immunology.

[3]  R. Ceredig,et al.  Mouse fetal thymus lobes cultured in IL-2 generate CD3+, TCR-gamma delta-expressing CD4-/CD8+ and CD4-/CD8- cells. , 1989, Journal of immunology.

[4]  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.

[5]  M. Toribio,et al.  Activation of the interleukin 2 pathway precedes CD3‐T cell receptor expression in thymic development. Differential growth requirements of early and mature intrathymic subpopulations , 1989, European journal of immunology.

[6]  D. Longo,et al.  Essential role of the interleukin 2-interleukin 2 receptor pathway in thymocyte maturation in vivo , 1988, The Journal of experimental medicine.

[7]  J. Allison,et al.  Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors , 1988, Nature.

[8]  M. Toribio,et al.  Human T‐Cell Precursors: Involvement of the IL‐2 Pathway in the Generation of Mature T Cells , 1988, Immunological reviews.

[9]  A. D'amico,et al.  Developmental Status and Reconstitution Potential of Subpopulations of Murine Thymocytes , 1988, Immunological reviews.

[10]  R. Ceredig.  Differentiation potential of 14-day fetal mouse thymocytes in organ culture. Analysis of CD4/CD8-defined single-positive and double-negative cells. , 1988, Journal of immunology.

[11]  Kendall A. Smith,et al.  Interleukin-2: inception, impact, and implications. , 1988, Science.

[12]  B. Haynes,et al.  Human thymic epithelial cells directly induce activation of autologous immature thymocytes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[13]  W. Paul,et al.  Proliferation and production of IL-2 and B cell stimulatory factor 1/IL-4 in early fetal thymocytes by activation through Thy-1 and CD3. , 1988, Journal of immunology.

[14]  T. Malek,et al.  The murine interleukin 2 receptor. Irreversible cross-linking of radiolabeled interleukin 2 to high affinity interleukin 2 receptors reveals a noncovalently associated subunit. , 1987, Journal of immunology.

[15]  E. Jenkinson,et al.  Importance of IL-2 receptors in intra-thymic generation of cells expressing T-cell receptors , 1987, Nature.

[16]  T. Mosmann,et al.  Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. , 1987, Journal of immunology.

[17]  R. Germain,et al.  Early genetic events in T cell development analyzed by in situ hybridization , 1987, The Journal of experimental medicine.

[18]  J. Bluestone,et al.  Identification of a monoclonal antibody specific for a murine T3 polypeptide. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[19]  K. Kato,et al.  Interleukin 2 high-affinity receptor expression requires two distinct binding proteins , 1987, The Journal of experimental medicine.

[20]  R. E. Cunningham,et al.  Cell growth cycle block of T cell hybridomas upon activation with antigen , 1987, The Journal of experimental medicine.

[21]  C. Pénit,et al.  Control of prothymocyte proliferation by thymic accessory cells , 1987, European journal of immunology.

[22]  P. Néve,et al.  Interleukin 2 , 1987, Acta clinica Belgica.

[23]  J. Lowenthal,et al.  Functional status of interleukin 2 receptors expressed by immature (Lyt-2-/L3T4-) thymocytes. , 1986, Journal of immunology.

[24]  R. Ceredig.  Proliferation in vitro and interleukin production by 14 day fetal and adult Lyt-2-/L3T4- mouse thymocytes. , 1986, Journal of immunology.

[25]  R. Coffman,et al.  Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. , 1986, Journal of immunology.

[26]  R. Gallo,et al.  Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Steinmetz,et al.  Detection of rearranged T cell receptor β‐chain gene and induction of cytolytic function in interleukin 2‐ responsive day 14–15 murine fetal thymocytes , 1986, European journal of immunology.

[28]  B. Fowlkes,et al.  Early T lymphocytes. Differentiation in vivo of adult intrathymic precursor cells , 1985, The Journal of experimental medicine.

[29]  R. Germain,et al.  Nucleotide sequence and expression of a mouse interleukin 2 receptor cDNA. , 1985, Journal of immunology.

[30]  T. Diamantstein,et al.  Developmentally controlled expression of IL 2 receptors and of sensitivity to IL 2 in a subset of embryonic thymocytes. , 1985, Journal of immunology.

[31]  J. Ashwell,et al.  Interleukin 2 upregulates expression of its receptor on a T cell clone , 1985, The Journal of experimental medicine.

[32]  A. Crisanti,et al.  Absence of growth by most receptor-expressing fetal thymocytes in the presence of interleukin-2 , 1985, Nature.

[33]  D. Raulet.  Expression and function of interleukin-2 receptors on immature thymocytes , 1985, Nature.

[34]  J. Lowenthal,et al.  Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells , 1985, Nature.

[35]  E. Shevach,et al.  Expression of interleukin 2 receptor on murine fetal thymocytes , 1985, European journal of immunology.

[36]  T. Taniguchi,et al.  Unique structure of murine interleukin-2 as deduced from cloned cDNAs , 1985, Nature.

[37]  E. Shevach,et al.  The murine IL 2 receptor. I. Monoclonal antibodies that define distinct functional epitopes on activated T cells and react with activated B cells. , 1984, Journal of immunology.

[38]  K. A. Wall,et al.  Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. , 1983, Journal of immunology.

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

[40]  T. Mandel,et al.  The differentiation of murine thymocytes in vivo and in vitro. , 1978, Immunology.

[41]  Kendall A. Smith,et al.  Long term culture of tumour-specific cytotoxic T cells , 1977, Nature.

[42]  F. Segal,et al.  A CHARACTERIZATION OF FIBRANT SEGAL CATEGORIES , 2006, math/0603400.