Abstract
Newborn BALB/c (Mls-1b) mice were intravenously injected with either bone marrow cells (BMC) or peritoneal exudate cells (PEC) from Mls semi-allogeneic (BALB/c x AKR)F1 mice. Thymic cells of these mice, obtained 7 days after the injection, were found to be unresponsive to the superantigen Mls-1a, as determined by graft-versus-host reactivity. On Day 7, deletion of T cells expressing the V beta 6 element at high levels (V beta 6hi) was observed in thymic cells of mice receiving PEC. In mice given BMC, it took 2 weeks until the proportion of V beta 6hi T cells began to decline, and a longer period was required for complete disappearance of V beta 6hi T cells. These results may indicate that although both BMC and PEC contain cells mediating tolerance, a component(s) of cells responsible for clonal deletion is deficient in BMC. Immunohistological investigation showed that on Day 7 donor type B cells were present in the thymus of mice that received PEC but absent from mice that received BMC, whereas cells expressing donor type class I as well as class II antigens were seen in both recipients. The presence of donor type B cells could be observed 8 weeks after injection of BMC. By this time, the deletion of V beta 6hi T cells was completed. These results indicate, collectively, that the tolerance of both anergy type and deletion type occurs in the naturally developing thymus, and suggest that the presence of B cells in the thymus might be required for clonal deletion.
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- Haskins K., Hannum C., White J., Roehm N., Kubo R., Kappler J., Marrack P. The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype. J Exp Med. 1984 Aug 1;160(2):452–471. doi: 10.1084/jem.160.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hengartner H., Odermatt B., Schneider R., Schreyer M., Wälle G., MacDonald H. R., Zinkernagel R. M. Deletion of self-reactive T cells before entry into the thymus medulla. Nature. 1988 Nov 24;336(6197):388–390. doi: 10.1038/336388a0. [DOI] [PubMed] [Google Scholar]
- Hosono M., Hosokawa T., Kina T., Katsura Y. Neonatal tolerance induction in the thymus to MHC-class II-associated antigens. III. Significance of hemopoietic stem cells for induction and maintenance of Mls tolerance by continuous supply of tolerance-inducing nonlymphocytes. Cell Immunol. 1987 Aug;108(1):162–174. doi: 10.1016/0008-8749(87)90201-2. [DOI] [PubMed] [Google Scholar]
- Hosono M., Katsura Y., Muramatsu S. Ontogeny of antigen-presenting activity of haptenized cells in mice: early development of syngeneic T cell-stimulatory cells in thymus. Immunology. 1984 Jan;51(1):161–168. [PMC free article] [PubMed] [Google Scholar]
- Hosono M., Katsura Y. Neonatal tolerance induction in the thymus to MHC-class II-associated antigens. II. Significance of MHC antigens in anti-Mls tolerance. Cell Immunol. 1986 Nov;103(1):11–18. doi: 10.1016/0008-8749(86)90063-8. [DOI] [PubMed] [Google Scholar]
- Hosono M., Kina T., Hosokawa T., Katsura Y. Neonatal tolerance induction in the thymus to MHC-class II-associated antigens. I. Preferential induction of tolerance to Mls antigens and resistance to allo-MHC antigens. Cell Immunol. 1986 Nov;103(1):1–10. doi: 10.1016/0008-8749(86)90062-6. [DOI] [PubMed] [Google Scholar]
- Inaba M., Inaba K., Hosono M., Kumamoto T., Ishida T., Muramatsu S., Masuda T., Ikehara S. Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells. J Exp Med. 1991 Mar 1;173(3):549–559. doi: 10.1084/jem.173.3.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Staerz U., White J., Marrack P. C. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature. 1988 Mar 3;332(6159):35–40. doi: 10.1038/332035a0. [DOI] [PubMed] [Google Scholar]
- Katsura Y., Kina T., Takaoki Y., Nishikawa S. Quantification of the progenitors for thymic T cells in various organs. Eur J Immunol. 1988 Jun;18(6):889–895. doi: 10.1002/eji.1830180609. [DOI] [PubMed] [Google Scholar]
- Kimoto H., Shirasawa T., Taniguchi M., Takemori T. B cell precursors are present in the thymus during early development. Eur J Immunol. 1989 Jan;19(1):97–104. doi: 10.1002/eji.1830190116. [DOI] [PubMed] [Google Scholar]
- Mazda O., Watanabe Y., Gyotoku J., Katsura Y. Requirement of dendritic cells and B cells in the clonal deletion of Mls-reactive T cells in the thymus. J Exp Med. 1991 Mar 1;173(3):539–547. doi: 10.1084/jem.173.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishikawa S., Sasaki Y., Kina T., Amagai T., Katsura Y. A monoclonal antibody against Igh6-4 determinant. Immunogenetics. 1986;23(2):137–139. doi: 10.1007/BF00377976. [DOI] [PubMed] [Google Scholar]
- Nossal G. J. Cellular mechanisms of immunologic tolerance. Annu Rev Immunol. 1983;1:33–62. doi: 10.1146/annurev.iy.01.040183.000341. [DOI] [PubMed] [Google Scholar]
- Payne J., Huber B. T., Cannon N. A., Schneider R., Schilham M. W., Acha-Orbea H., MacDonald H. R., Hengartner H. Two monoclonal rat antibodies with specificity for the beta-chain variable region V beta 6 of the murine T-cell receptor. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7695–7698. doi: 10.1073/pnas.85.20.7695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsdell F., Lantz T., Fowlkes B. J. A nondeletional mechanism of thymic self tolerance. Science. 1989 Nov 24;246(4933):1038–1041. doi: 10.1126/science.2511629. [DOI] [PubMed] [Google Scholar]
- Roberts J. L., Sharrow S. O., Singer A. Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities. J Exp Med. 1990 Mar 1;171(3):935–940. doi: 10.1084/jem.171.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneider R., Lees R. K., Pedrazzini T., Zinkernagel R. M., Hengartner H., MacDonald H. R. Postnatal disappearance of self-reactive (V beta 6+) cells from the thymus of Mlsa mice. Implications for T cell development and autoimmunity. J Exp Med. 1989 Jun 1;169(6):2149–2158. doi: 10.1084/jem.169.6.2149. [DOI] [PMC free article] [PubMed] [Google Scholar]



