This report describes T cell lines derived from a patient with subacute cutaneous lupus after treatment with intravenous pulse cyclophosphamide. We selected for mitotically active, hypoxanthine-guanine phosphoribosyltransferase-deficient (HPRT -) T cells, by culture in a selective medium containing 6-thioguanine. When HPRT-cell lines were derived 6 days after pulse cyclophosphamide (CYC) treatment, they were predominantly CD8+ and T cell receptor (TCR) y/S+, producing interferon-y (IFNy). Cell lines derived 21 days after CYC treatment were CD4+, TCRdP+ and produced both IFNy and interleukin-4. These results support a possible role for y/S+ T cells in subacute cutaneous lupus and suggest a mechanism for the therapeutic effect of CYC.
Systemic lupus erythematosus (SLE) is an autoimmune multisystem inflammatory disorder characterized by the production of antibodies that react with multiple self antigens (1). Although the exact etiology of the disease in unknown, evidence implicates both T cells and B cells in the pathogenesis of SLE. Previous data from our laboratory support the hypothesis that T cells are involved, as demonstrated by increased in vivo division and/or survival (2).
The present work was based on earlier studies of hypoxanthine-guanine phosphoribosyltransferase (HPRT), an enzyme associated with the purine salvage pathway. Deficiency of HPRT (HPRT-) is easily detected by the absence of cell growth in cultures Dr.