Isolation and functional characterization of IL-2 responsive T cell clones from NZB x NZW F1 mice.
Autoantigen-reactive T cells might play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Autoantigen-reactive T cell clones were generated from spleens of NZB x NZW F1 (BWF1) and normal control BALB/c mice with interleukin-2 (IL-2), a procedure that selects for in vivo activated antigen-reactive T cells. The antigen-specificity of the T cell clones was tested by using a panel of candidate autoantigens. The T cell clones from BWF1 mice but not those from BALB/c mice proliferated against heparan sulfate, the major glycosaminoglycan of glomerular basement membrane. None of the clones proliferated against dsDNA or cardiolipin. All the heparan sulfate-reactive T cell clones had the ability to selectively augment the production of IgG anti-dsDNA autoantibodies. When cultured with either heparan sulfate or Concanavalin A, the T cell clones produced high levels of IL-4 and IL-5 with no detectable IL-2 or IFN-gamma. In contrast, T cell clones derived from BALB/c mice augmented the production of total polyclonal IgG but not the production of anti-dsDNA antibodies. These studies indicate the existence of heparan sulfate-reactive T cells in BWF1 mice. Characterization of heparan sulfate-reactive T cells that could selectively augment anti-dsDNA production will permit the design of targeted and antigen-specific therapy.
Ofosu-Appiah
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W
Department of immunology, Masonic Medical-Research Laboratory, Utica, NY 13501, USA.
Aiello
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V
Sfeir
G
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Viti
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D
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D002469:Cell Separation; D002999:Clone Cells; D000939:Epitopes; D005260:Female; D006497:Heparan Sulfate / Q000494:pharmacology; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D000939:Epitopes; D006497:Heparan Sulfate; D007376:Interleukin-2