Identification of a Novel Thymocyte Growth Factor Derived from B Cell Lymphomas
T cell ontogeny is a rapidly developing area. However, the signals that mediate the differentiation and growth of immature T cells in the thymus through different maturational stages remain largely unknown. While much has been accomplished in understanding the role that molecules of the major histocompatibility complex have in the process of selection of the T cell repertoire,1,2 little is known about the role that cytokines may play in these processes. Most of these studies have focused on IL-2;3,4 however, its role in T cell ontogeny is still controversial. More recently, it has been observed that IL-4 can induce thymocyte growth in combination with phorbol ester (PMA).5,6 Other cytokines that have been shown to have thymocyte growth factor properties include IL-1,7 IL-6,8,9 IL-7,10 TNFa,11,12 and in fetal thymocytes (day 15 of gestation) P40 (IL-9)13 and GM-CSF.14 Many of these cytokines have been shown to be produced by thymocytes and/or thymic stromal cells as well,13,15 suggesting that they play a role in T cell ontogeny. We have been exploring the response patterns of adult murine thymocyte subsets separated on the basis of their expression of CD3, CD4 and CD8, and in fetal thymocytes at day 15 of gestation. An important conclusion from these studies is that the growth-promoting effects of some of these cytokines are specific for certain thymocyte subsets. For example, IL-1 is specific for the CD3+4-8- subset while IL-6 is specific for the CD4+8- and CD4-8+ subsets.8,12 These studies have shown that very few cytokine combinations induce the proliferation of the most immature thymocyte subset: CD3-4-8- thymocytes.12 Therefore, we have endeavored to find other novel cytokines that may activate this subset.
KeywordsCell Lymphoma Single Positive Immature Thymocyte Inhibit Cytokine Production Thymic Stromal Cell
Unable to display preview. Download preview PDF.
- 15.J. Ransom, M. Fischer, T. Mosmann, T. Yokota, D. DeLuca, J. Schumacher, and A. Zlotnik, Interferon-is produced by activated immature thymocytes: Effects on la induction on thymic epithelial cells and on interleukin-4-mediated immature thymocyte proliferation, J. Immunol. 139:4102 (1987).PubMedGoogle Scholar
- 16.P. Willoughby, J. Jenette, and G. Haughton, Analysis of a murine B cell lymphoma, CH44, with an associated non-neoplastic T cell population. I. Proliferation of normal T lymphocytes is induced by a secreted product of the malignant B cells, J. Pathol. 133:507 (1988).Google Scholar
- 19.A. O’Garra, G. Stapleton, V. Dhar, M. Pearce, J. Schumacher, H. Rugo, D. Barbis, A. Stall, J. Cupp, K. Moore, P. Vieira, T. Mossman, A. Whitmore, L. Arnold, G. Haughton, and M. Howard, Production of known and novel cytokines by mouse B lymphomas and normal Ly-l+ B cells Internat. Immunol ,(in press).Google Scholar
- 20.I. MacNeil, T. Suda, K. Moore, T. Mossman, and A. Zlotnik, Interleukin 10: A novel cytokine growth cofactor for mature and immature murine lymphocytes (submitted for publication).Google Scholar