Abstract
T-like cells from congenitally athymic nude rats of the PVG (RT1c) strain were characterized both phenotypically and functionally. There was an age-dependent increase in the number of alpha beta TcR+CD3+ cells in the lymph nodes, spleen and thoracic duct of nude rats. These cells, which comprised up to 25% of lymph node cells in animals of 8-12 months in age, were also CD3+CD5+Thy-1.1-. The expression of CD4 and CD8 on T-like cells was mutually exclusive. Approximately 30% of the CD4+ cells expressed CD45RB and 50% of the TcR+ cells expressed RT6. B-cell-depleted TcR+ cells from nude animals gave proliferative responses to mitogenic lectins or immobilized anti-CD3 antibody. T-like cells showed comparable alloreactivity to their euthymic counterparts in mixed lymphocyte reactions (MLR) against three different MHC haplotypes and to lymphocytes of a congenic strain differing only in MHC-encoded products. Monoclonal antibodies (mAb) to CD4, MHC class II, alpha beta TcR and CD3 blocked the MLR. However, T-like cells failed to induce rejection of skin allografts of the same MHC haplotypes when adoptively transferred to athymic nude hosts and were unable to mount a normal graft-versus-host (GVH) response. These results indicate that lymphocytes may rearrange and express a functional TcR in the absence of a thymus, but that the thymic microenvironment is essential for T cells to acquire full in vivo function.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ager A., Fajumi J., Sparshott S. M., Ford W. L., Butcher G. W. Major histocompatibility complex control of NK-related allogeneic lymphocyte cytotoxicity in rats. The contributions of strong and medial transplantation antigens. Transplantation. 1988 Nov;46(5):762–767. doi: 10.1097/00007890-198811000-00025. [DOI] [PubMed] [Google Scholar]
- Bell E. B., Sparshott S. M., Drayson M. T., Ford W. L. The stable and permanent expansion of functional T lymphocytes in athymic nude rats after a single injection of mature T cells. J Immunol. 1987 Sep 1;139(5):1379–1384. [PubMed] [Google Scholar]
- Bell E. B., Sparshott S. M., Drayson M. T., Hunt S. V. The origin of T cells in permanently reconstituted old athymic nude rats. Analysis using chromosome or allotype markers. Immunology. 1989 Dec;68(4):547–556. [PMC free article] [PubMed] [Google Scholar]
- Bell E. B., Sparshott S. M. Interconversion of CD45R subsets of CD4 T cells in vivo. Nature. 1990 Nov 8;348(6297):163–166. doi: 10.1038/348163a0. [DOI] [PubMed] [Google Scholar]
- Bell E. B. Thymus-derived and non-thymus-derived T-like cells: the origin and function of cells bearing gamma delta receptors. Thymus. 1989;14(1-3):3–17. [PubMed] [Google Scholar]
- Festing M. F., May D., Connors T. A., Lovell D., Sparrow S. An athymic nude mutation in the rat. Nature. 1978 Jul 27;274(5669):365–366. doi: 10.1038/274365a0. [DOI] [PubMed] [Google Scholar]
- Finkel T. H., Marrack P., Kappler J. W., Kubo R. T., Cambier J. C. Alpha beta T cell receptor and CD3 transduce different signals in immature T cells. Implications for selection and tolerance. J Immunol. 1989 May 1;142(9):3006–3012. [PubMed] [Google Scholar]
- Ford W. L., Rolstad B., Fossum S., Hunt S. V., Smith M. E., Sparshott S. M. The stimulus to host cell proliferation in graft-versus-host reactions. Scand J Immunol. 1981 Dec;14(6):705–713. doi: 10.1111/j.1365-3083.1981.tb00613.x. [DOI] [PubMed] [Google Scholar]
- Fry A. M., Jones L. A., Kruisbeek A. M., Matis L. A. Thymic requirement for clonal deletion during T cell development. Science. 1989 Nov 24;246(4933):1044–1046. doi: 10.1126/science.2511630. [DOI] [PubMed] [Google Scholar]
- Gracie J. A., Sarawar S. R., Bolton E. M., Bradley J. A., Tanaka T., Bell E. B. Renal allograft rejection in CD4+ T cell-reconstituted athymic nude rats. The origin of CD4+ and CD8+ graft-infiltrating cells. Transplantation. 1990 Dec;50(6):996–1000. doi: 10.1097/00007890-199012000-00020. [DOI] [PubMed] [Google Scholar]
- Hodes R. J., Sharrow S. O., Solomon A. Failure of T cell receptor V beta negative selection in an athymic environment. Science. 1989 Nov 24;246(4933):1041–1044. doi: 10.1126/science.2587987. [DOI] [PubMed] [Google Scholar]
- Kindred B., Bösing-Schneider R., Corley R. B. In vivo activity of a nonspecific T cell-replacing factor. J Immunol. 1979 Jan;122(1):350–354. [PubMed] [Google Scholar]
- Kindred B. Immunological unresponsiveness of genetically thymusless (nude) mice. Eur J Immunol. 1971 Jan;1(1):59–61. doi: 10.1002/eji.1830010114. [DOI] [PubMed] [Google Scholar]
- Kishihara K., Yoshikai Y., Matsuzaki G., Mak T. W., Nomoto K. Functional alpha and beta T cell chain receptor messages can be detected in old but not in young athymic mice. Eur J Immunol. 1987 Apr;17(4):477–482. doi: 10.1002/eji.1830170407. [DOI] [PubMed] [Google Scholar]
- Kung J. T. Impaired clonal expansion in athymic nude CD8+CD4- T cells. J Immunol. 1988 Jun 1;140(11):3727–3735. [PubMed] [Google Scholar]
- Kung J. T., Thomas C. A., 3rd Athymic nude CD4+8- T cells produce IL-2 but fail to proliferate in response to mitogenic stimuli. J Immunol. 1988 Dec 1;141(11):3691–3696. [PubMed] [Google Scholar]
- Lawetzky A., Tiefenthaler G., Kubo R., Hünig T. Identification and characterization of rat T cell subpopulations expressing T cell receptors alpha/beta and gamma/delta. Eur J Immunol. 1990 Feb;20(2):343–349. doi: 10.1002/eji.1830200217. [DOI] [PubMed] [Google Scholar]
- MacDonald H. R., Lees R. K., Bron C., Sordat B., Miescher G. T cell antigen receptor expression in athymic (nu/nu) mice. Evidence for an oligoclonal beta chain repertoire. J Exp Med. 1987 Jul 1;166(1):195–209. doi: 10.1084/jem.166.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDonald H. R., Lees R. K., Glasebrook A. L., Sordat B. Interleukin 2 production by lymphoid cells from congenitally athymic (nu/nu) mice. J Immunol. 1982 Aug;129(2):521–525. [PubMed] [Google Scholar]
- MacDonald H. R., Lees R. K., Sordat B., Zaech P., Maryanski J. L., Bron C. Age-associated increase in expression of the T cell surface markers Thy-1, Lyt-1, and Lyt-2 in congenitally athymic (nu/nu) mice: analysis by flow microfluorometry. J Immunol. 1981 Mar;126(3):865–870. [PubMed] [Google Scholar]
- Maleckar J. R., Sherman L. A. The composition of the T cell receptor repertoire in nude mice. J Immunol. 1987 Jun 1;138(11):3873–3876. [PubMed] [Google Scholar]
- Mojcik C. F., Greiner D. L., Medlock E. S., Komschlies K. L., Goldschneider I. Characterization of RT6 bearing rat lymphocytes. I. Ontogeny of the RT6+ subset. Cell Immunol. 1988 Jul;114(2):336–346. doi: 10.1016/0008-8749(88)90326-7. [DOI] [PubMed] [Google Scholar]
- Pantelouris E. M. Observations on the immunobiology of 'nude' mice. Immunology. 1971 Feb;20(2):247–252. [PMC free article] [PubMed] [Google Scholar]
- Pennycuik P. R. Unresponsiveness of nude mice to skin allografts. Transplantation. 1971 Apr;11(4):417–418. doi: 10.1097/00007890-197104000-00012. [DOI] [PubMed] [Google Scholar]
- Powrie F., Mason D. Phenotypic and functional heterogeneity of CD4+ T cells. Immunol Today. 1988 Sep;9(9):274–277. doi: 10.1016/0167-5699(88)91309-6. [DOI] [PubMed] [Google Scholar]
- Raff M. C. Theta-bearing lymphocytes in nude mice. Nature. 1973 Dec 7;246(5432):350–351. doi: 10.1038/246350a0. [DOI] [PubMed] [Google Scholar]
- Rolstad B., Ford W. L. The rapid elimination of allogeneic lymphocytes: relationship to established mechanisms of immunity and to lymphocyte traffic. Immunol Rev. 1983;73:87–113. doi: 10.1111/j.1600-065x.1983.tb01080.x. [DOI] [PubMed] [Google Scholar]
- Rygaard J. Immunobiology of the mouse mutant "Nude". Preliminary investigations. Acta Pathol Microbiol Scand. 1969;77(4):761–762. [PubMed] [Google Scholar]
- Schuurman H. J., Vaessen L. M., Broekhuizen R., Brandt C. J., Holewijn M. C., Vos J. G., Rozing J. Implantation of cultured thymic fragments in congenitally athymic (nude) rats. Influx of lymphocytes and dendritic cells. Scand J Immunol. 1987 Aug;26(2):129–139. doi: 10.1111/j.1365-3083.1987.tb02245.x. [DOI] [PubMed] [Google Scholar]
- Schwinzer R., Hedrich H. J., Wonigeit K. T cell differentiation in athymic nude rats (rnu/rnu): demonstration of a distorted T cell subset structure by flow cytometry analysis. Eur J Immunol. 1989 Oct;19(10):1841–1847. doi: 10.1002/eji.1830191013. [DOI] [PubMed] [Google Scholar]
- Sparshott S. M., Bell E. B., Sarawar S. R. CD45R CD4 T cell subset-reconstituted nude rats: subset-dependent survival of recipients and bi-directional isoform switching. Eur J Immunol. 1991 Apr;21(4):993–1000. doi: 10.1002/eji.1830210420. [DOI] [PubMed] [Google Scholar]
- Spickett G. P., Brandon M. R., Mason D. W., Williams A. F., Woollett G. R. MRC OX-22, a monoclonal antibody that labels a new subset of T lymphocytes and reacts with the high molecular weight form of the leukocyte-common antigen. J Exp Med. 1983 Sep 1;158(3):795–810. doi: 10.1084/jem.158.3.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tanaka T., Masuko T., Yagita H., Tamura T., Hashimoto Y. Characterization of a CD3-like rat T cell surface antigen recognized by a monoclonal antibody. J Immunol. 1989 Apr 15;142(8):2791–2795. [PubMed] [Google Scholar]
- Vaessen L. M., Broekhuizen R., Rozing J., Vos J. G., Schuurman H. J. T-cell development during ageing in congenitally athymic (nude) rats. Scand J Immunol. 1986 Aug;24(2):223–235. doi: 10.1111/j.1365-3083.1986.tb02089.x. [DOI] [PubMed] [Google Scholar]
- Vos J. G., Kreeftenberg J. G., Kruijt B. C., Kruizinga W., Steerenberg P. The athymic nude rat. II. Immunological characteristics. Clin Immunol Immunopathol. 1980 Feb;15(2):229–237. doi: 10.1016/0090-1229(80)90033-1. [DOI] [PubMed] [Google Scholar]
- Wagner H., Hardt C., Heeg K., Röllinghoff M., Pfizenmaier K. T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice. Nature. 1980 Mar 20;284(5753):278–278. doi: 10.1038/284278a0. [DOI] [PubMed] [Google Scholar]
- Whitby E. H., Sparshott S. M., Bell E. B. Allograft rejection in athymic nude rats by transferred T-cell subsets. I. The response of naive CD4+ and CD8+ thoracic duct lymphocytes to complete allogeneic incompatibilities. Immunology. 1990 Jan;69(1):78–84. [PMC free article] [PubMed] [Google Scholar]
- Williams A. F. Many cells in rat bone marrow have cell-surface Thy-1 antigen. Eur J Immunol. 1976 Jul;6(7):526–528. doi: 10.1002/eji.1830060716. [DOI] [PubMed] [Google Scholar]
- Wortis H. H. Immunological responses of 'nude' mice. Clin Exp Immunol. 1971 Feb;8(2):305–317. [PMC free article] [PubMed] [Google Scholar]