Deletion of self-reactive T cells in nude mice grafted with neonatal allogeneic thymus

H. Yuuki, Y. Yoshikai, K. Kishihara, A. Iwasaki, G. Matsuzaki, M. Ogimoto, K. Nomoto

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    Abstract

    The cellular basis of tolerance induction has been investigated in BALB/c(H-2(d),Thy1.2,Mls1b2a) nude mice grafted with thymus of neonatal AKR/J mice(H-2(k),Thy1.1,Mls1a2b). The spleen cells from nude mice grafted with AKR/J thymus showed a significantly decreased level of primary cytotoxic T cell response when stimulated with AKR/J cells, although these cells lysed well target cells of a third party C57BL/6 when stimulated with C57BL/6 cells. Consistent with CTL responses, T cells bearing V(β)6, that is important for recognizing Mls1a-encoded products of the thymic phenotype, were virtually abolished in the spleen and lymph node cells of nude mice 8 wk after grafting with AKR/J thymus. However, a substantial number of V(β)6-bearing T cells were detected in the peripheral organs of nude mice 23 wk after grafting with AKR/J thymus and in those of nude mice grafted with AKR/J fetal thymus depleted of macrophages/dendritic cells by incubating with 2'-deoxyguanosine in vitro before grafting. On the other hand, T cells bearing V(β)3, which are selectively related to Mls2a-encoded products of the host phenotype, were expressed neither on the peripheral T cells of nude mice grafted with AKR/J thymus at any stage after grafting nor on those of nude mice grafted with 2'-deoxyguanosine-treated AKR/J thymus. These data suggested that both V(β)6 and V(β)3 T cells were eliminated in the thymus of nude mice grafted with AKR/J thymus, presumably on the basis of interaction with both of graft-derived persisting and host-derived hemopoietic cells in the thymus and that thymic epithelium appears to have little capacity to eliminate T cells reactive to minor lymphocyte stimulating-encoded products.

    Original languageEnglish
    Pages (from-to)474-479
    Number of pages6
    JournalJournal of Immunology
    Volume144
    Issue number2
    Publication statusPublished - 1990

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    Nude Mice
    Thymus Gland
    T-Lymphocytes
    Deoxyguanosine
    Spleen
    Inbred AKR Mouse
    Phenotype
    Dendritic Cells
    Epithelium
    Lymph Nodes
    Macrophages
    Lymphocytes
    Transplants

    All Science Journal Classification (ASJC) codes

    • Immunology

    Cite this

    Yuuki, H., Yoshikai, Y., Kishihara, K., Iwasaki, A., Matsuzaki, G., Ogimoto, M., & Nomoto, K. (1990). Deletion of self-reactive T cells in nude mice grafted with neonatal allogeneic thymus. Journal of Immunology, 144(2), 474-479.

    Deletion of self-reactive T cells in nude mice grafted with neonatal allogeneic thymus. / Yuuki, H.; Yoshikai, Y.; Kishihara, K.; Iwasaki, A.; Matsuzaki, G.; Ogimoto, M.; Nomoto, K.

    In: Journal of Immunology, Vol. 144, No. 2, 1990, p. 474-479.

    Research output: Contribution to journalArticle

    Yuuki, H, Yoshikai, Y, Kishihara, K, Iwasaki, A, Matsuzaki, G, Ogimoto, M & Nomoto, K 1990, 'Deletion of self-reactive T cells in nude mice grafted with neonatal allogeneic thymus', Journal of Immunology, vol. 144, no. 2, pp. 474-479.
    Yuuki H, Yoshikai Y, Kishihara K, Iwasaki A, Matsuzaki G, Ogimoto M et al. Deletion of self-reactive T cells in nude mice grafted with neonatal allogeneic thymus. Journal of Immunology. 1990;144(2):474-479.
    Yuuki, H. ; Yoshikai, Y. ; Kishihara, K. ; Iwasaki, A. ; Matsuzaki, G. ; Ogimoto, M. ; Nomoto, K. / Deletion of self-reactive T cells in nude mice grafted with neonatal allogeneic thymus. In: Journal of Immunology. 1990 ; Vol. 144, No. 2. pp. 474-479.
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    abstract = "The cellular basis of tolerance induction has been investigated in BALB/c(H-2(d),Thy1.2,Mls1b2a) nude mice grafted with thymus of neonatal AKR/J mice(H-2(k),Thy1.1,Mls1a2b). The spleen cells from nude mice grafted with AKR/J thymus showed a significantly decreased level of primary cytotoxic T cell response when stimulated with AKR/J cells, although these cells lysed well target cells of a third party C57BL/6 when stimulated with C57BL/6 cells. Consistent with CTL responses, T cells bearing V(β)6, that is important for recognizing Mls1a-encoded products of the thymic phenotype, were virtually abolished in the spleen and lymph node cells of nude mice 8 wk after grafting with AKR/J thymus. However, a substantial number of V(β)6-bearing T cells were detected in the peripheral organs of nude mice 23 wk after grafting with AKR/J thymus and in those of nude mice grafted with AKR/J fetal thymus depleted of macrophages/dendritic cells by incubating with 2'-deoxyguanosine in vitro before grafting. On the other hand, T cells bearing V(β)3, which are selectively related to Mls2a-encoded products of the host phenotype, were expressed neither on the peripheral T cells of nude mice grafted with AKR/J thymus at any stage after grafting nor on those of nude mice grafted with 2'-deoxyguanosine-treated AKR/J thymus. These data suggested that both V(β)6 and V(β)3 T cells were eliminated in the thymus of nude mice grafted with AKR/J thymus, presumably on the basis of interaction with both of graft-derived persisting and host-derived hemopoietic cells in the thymus and that thymic epithelium appears to have little capacity to eliminate T cells reactive to minor lymphocyte stimulating-encoded products.",
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