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Persistent expression of a soluble form of Fas/APO1 in continuously activated T cells from a patient with SLE
B Kovacs1, T Szentendrei, J M Bednarek
1Department of Clinical Physiology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Objective:
To report a patient with SLE whose T cells expressed disproportionally increased amounts of an alternatively spliced form of Fas/APO1 transcript and secreted a soluble form of Fas.
Methods:
We established continuously activated, short-term T cell lines from 16 patients with SLE and from 6 normal controls. The structure, expression and function 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 dominant product of the Fas-gene in one line (S18B) derived from a patient with very active SLE. Compared to a control line, the S18B cells displayed decreased surface Fas expression but increased accumulation of Fas inside the cell. The amount of soluble Fas in the culture supernatant of S18B was found to be 1.8 times higher than that of a control line. Culture supernatants from S18B cells inhibited anti-Fas mAb-medicated T cell death.
Conclusion:
Continuously activated T cells from one patient with SLE displayed increased amounts of soluble Fas that inhibits anti-Fas mediated cell death. Although the frequency of this abnormality among patients with SLE and other diseases is unknown, increased production of soluble Fas may have contributed to the pathogenesis of SLE in the patient presented here.