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

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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 - 1991

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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