Suppression and reversal of gld disease by parabiosis with normal mice.
The disruption of the Fas receptor or Fas ligand by the lpr or gld mutations, 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 that gld-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 reversing gld-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 in gld mice parabiosed with normal mice at 4-6 weeks of age. The gld mice 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 to gld mice parabiosed with gld mice. In contrast, older lpr mice did not exhibit any reduction in lymphadenopathy or autoantibody production after parabiosis with normal mice. The prevention or reversal of lymphadenopathy in parabiosed gld mice 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 parabiosed gld mice suggests that autoantibody-producing B cells or their committed precursors are long lived and do not express functional Fas receptor.
Kakkanaiah
V N
VN
Department of Medicine, University of North Carolina at Chapel Hill 27599-7280, USA.
MacDonald
G C
GC
Cohen
P L
PL
Eisenberg
R A
RA
D000367:Age Factors; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D005260:Female; D007165:Immunosuppression Therapy; D008198:Lymph Nodes / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010227:Parabiosis; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology / Q000628:therapy
D001323:Autoantibodies