Suppression and Reversal ofgldDisease by Parabiosis with Normal Mice

• Published in: Clinical immunology and immunopathology 1996-01, Vol.78 (1), p.6-13
• Main Authors: Kakkanaiah, Vellalore N., MacDonald, Glen C., Cohen, Philip L., Eisenberg, Robert A.
• Format: Article
• Language: English
• ISSN: 0090-1229; 1090-2341
• DOI: 10.1006/clin.1996.0002

The disruption of the Fas receptor or Fas ligand by thelprorgldmutations, respectively, results in severe autoimmune and lymphoproliferative disease due to the failure of Fas-mediated deletion of self-reactive lymphocytes. Recently, we have shown in mixed chimeras thatgld-induced autoimmunity could be corrected by normal bone marrow, in particular by normal T cells. In contrast,lpr-mediated autoimmunity could not be influenced by normal bone marrow-derived cells. In the present report, we have studied the role of normal lymphocytes in suppressing or reversinggld-induced autoimmunity by parabiosis with normal mice. Our results show a suppression of lymphadenopathy, fewer CD4−CD8−T cells, and lower levels of autoantibody production ingldmice parabiosed with normal mice at 4–6 weeks of age. Thegldmice parabiosed with normal mice at 4 months of age also exhibited a substantial reduction of both total and CD4−CD8−T cells in the periphery 2 months after surgery. However, they showed little reduction of autoantibodies compared togldmice parabiosed withgldmice. In contrast, olderlprmice did not exhibit any reduction in lymphadenopathy or autoantibody production after parabiosis with normal mice. The prevention or reversal of lymphadenopathy in parabiosedgldmice suggests that ongoing Fas-mediated deletion in the periphery may play an important role in maintaining self-tolerance. The relative irreversibility of autoantibody synthesis in older parabiosedgldmice suggests that autoantibody-producing B cells or their committed precursors are long lived and do not express functional Fas receptor.