The investigators have described a new murine model of human SLE. By injection of pristane into BALB/c mice, these mice develop IgM anti-DNA and anti-histone antibodies followed by IgG antibodies with specificities similar to human SLE. They propose that the initial autoantibodies are T-cell-independent and the IgG autoantibodies that develop later, are T-cell-dependent. In the first specific aim, the investigators will study which T-cell subpopulations are responsible for late autoantibody production. They will evaluate autoantibody production in a variety of knock-out mice including B2m, class II, TAP I, CD4, CD8, and specific TCR. In the second specific aim, they will investigate the role of Th1 and Th2 cytokines as they relate to pristane-induced autoantibody production. Cytokines will be quantified by RT-PCR as well as ELISAs. Cytokine examination will be performed in concert with the gene knock-out studies in Specific Aim 1 to determine whether a specific T-cell subset or cytokine is more critical for autoantibody production.
In Aim 3, the investigators will quantify the cytokines produced by macrophages, IL-1, IL-6 and TNF-a. In addition, they will also test whether LPS accelerates autoantibody production. To examine the effect of pristane on T-cell tolerance, pristane will be administered to mice previously immunized with the superantigen, SEB. The numbers of responding cells as well as the production of IL-2 and IL-4 will be quantified.
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