PERSISTENT EXPRESSION OF A SOLUBLE FORM OF FAS APO1 IN CONTINUOUSLY ACTIVATED T-CELLS FROM A PATIENT WITH SLE/

Objective: To report a patient with SLE whose T cells expressed dispro portionally increased amounts of an alternatively spliced form of Fas/ APO1 transcript and secreted a soluble form of Fas. Methods: We establ ished continuously activated, short-term T cell lines from 16 patients with SLE and from 6 normal controls. The structure, expression and fu nction of Fas was examined using RT-PCR and sequencing, flow cytometry (surface expression of Fas), ELISA (measurement of soluble Fas) and a PI-based cytotoxicity assay (functional analysis). Results: A soluble form of Fas which originates from an alternatively spliced transcript and lacks the transmembrane domain of the original molecule was the d ominant product of the Fas-gene in one line (S18B) derived from a pati ent with very active SLE. Compared to a control line, the S18B cells d isplayed decreased surface Fas expression but increased accumulation o f Fas inside the cell. The amount of soluble Fas in the culture supema tant of S18B was found to be 1.8 times higher than that of a control l ine. Culture supernatants from S18B cells inhibited anti-Fas mAb-media ted T cell death. Conclusion: Continuously activated T cells from one patient with SLE displayed increased amounts of soluble Fas that inhib its anti-Fas mediated cell death. Although the frequency of this abnor mality among patients with SLE and other diseases is unknown, increase d production of soluble Fas may have contributed to the pathogenesis o f SLE in the patient presented here.