ISOLATION AND FUNCTIONAL-CHARACTERIZATION OF IL-2 RESPONSIVE T-CELL CLONES FROM NZBX NZW F1-MICE

Autoantigen-reactive T cells might play an important role in the patho genesis of systemic lupus erythematosus (SLE). Autoantigen-reactive T cell clones were generated from spleens of NZBxNZW F1 (BWF1) and norma l control BALB/c mice with interleukin-2 (IL-2), a procedure that sele cts for in vivo activated antigen-reactive T cells. The antigen-specif icity of the T cell clones was tested by using a panel of candidate au toantigens. The T cell clones from BWF1 mice but not those from BALB/c mice proliferated against heparan sulfate, the major glycosaminoglyca n of glomerular basement membrane. None of the clones proliferated aga inst dsDNA or cardiolipin. All the heparan sulfate-reactive T cell clo nes had the ability to selectively augment the production of IgG anti- dsDNA autoantibodies. When cultured with either heparan sulfate or Con canavalin A, the T cell clones produced high levels of IL-4 and IL-5 w ith no detectable IL-2 or IFN-gamma. In contrast, T cell clones derive d from BALB/c mice augmented the production of total polyclonal IgG bu t not the production of anti-dsDNA antibodies. These studies indicate the existence of heparan sulfate-reactive T cells in BWF1 mice. Charac terization of heparan sulfate-reactive T cells that could selectively augment anti-dsDNA production will permit the design of targeted and a ntigen-specific therapy. (C) 1996 Academic Press Limited