Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus

K. Matsumoto, Y. Yoshikai, T. Asano, K. Himeno, A. Iwasaki, K. Nomoto

    Research output: Contribution to journalArticle

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    Abstract

    Transplantation of bone marrow cells of lpr/lpr mice into irradiated normal mice fails to develop massive lymphadenopathy or autoimmunity but causes severe graft-vs.-host-like syndrome. To elucidate an abnormality of lpr/lpr bone marrow-derived T cells, we transplanted bone marrow cells of Mlsb lpr/lpr mice into H-2-compatible Mlsa non-lpr mice. Although lpr/lpr T cell precursors repopulated the host thymus as well as +/+ cells, a proportion of CD4+CD8+ cells decreased, and that of both CD4- and CD8- single-positive cells increased compared with those of +/+ recipients. Notably, in MRL/lpr → AKR and C3H/lpr → AKR chimeras, CD4 single-positive thymocytes contained an increased number of Vβ6+ cells in spite of potentially deleting alleles of Mlsa, whereas Vβ6+ mature T cells were deleted in the MRL/+ → AKR and C3H/+ → AKR chimeras. There was no difference between MRL/+ → AKR and MRL/lpr → AKR chimeras in their proportion of Vβ3+ cells because both host and donor strain lack the deleting alleles. Interleukin 2 receptor expression of mature T cells, in the thymus and lymph node, was obviously higher in the MRL/lpr → AKR chimeras, in particular in the 'forbidden' Vβ6+ subset. Moreover, lpr donor-derived peripheral T cells showed vigorous anti-CD3 response. These results indicate that lpr-derived T cells escape not only tolerance-related clonal deletion but also some induction of unresponsiveness in the non-lpr thymus.

    Original languageEnglish
    Pages (from-to)127-136
    Number of pages10
    JournalJournal of Experimental Medicine
    Volume173
    Issue number1
    DOIs
    Publication statusPublished - Jan 25 1991

    Fingerprint

    Thymus Gland
    T-Lymphocytes
    Alleles
    Clonal Deletion
    T-Lymphoid Precursor Cells
    Interleukin-2 Receptors
    Thymocytes
    Bone Marrow Transplantation
    Autoimmunity
    Bone Marrow Cells
    Cell Count
    Lymph Nodes
    Bone Marrow
    Transplants

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus. / Matsumoto, K.; Yoshikai, Y.; Asano, T.; Himeno, K.; Iwasaki, A.; Nomoto, K.

    In: Journal of Experimental Medicine, Vol. 173, No. 1, 25.01.1991, p. 127-136.

    Research output: Contribution to journalArticle

    Matsumoto, K, Yoshikai, Y, Asano, T, Himeno, K, Iwasaki, A & Nomoto, K 1991, 'Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus', Journal of Experimental Medicine, vol. 173, no. 1, pp. 127-136. https://doi.org/10.1084/jem.173.1.127
    Matsumoto, K. ; Yoshikai, Y. ; Asano, T. ; Himeno, K. ; Iwasaki, A. ; Nomoto, K. / Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus. In: Journal of Experimental Medicine. 1991 ; Vol. 173, No. 1. pp. 127-136.
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