In vitro effects of immunosuppressive agents on cytokine production by HTLV-I-infected T cell clones derived from the ocular fluid of patients with HTLV-I uveitis.

Abstract

The present study was designed to investigate the in vitro effects of potential therapeutic agents on cytokine production by five HTVL-I-infected T cell clones (TCC) established from the ocular fluid of patients with HTLV-I uveitis. Each of the five HTLV-I-infected TCC was cultured at 1 x 10(6) cells/ml with or without an immunosuppressive agent (hydrocortisone, FK506, rapamycin, indomethacin, or prostaglandin E2) for 22 hr in humidified 5% CO2 in air at 37 C. The production of various cytokines in the culture supernatant from each TCC was measured by ELISA. The HTLV-I-infected TCC produced high amounts of IL-1 alpha, IL-3, IL-6, IL-8, TNF-alpha, IFN-gamma, and GM-CSF, and low but significant levels of IL-2 and IL-10 without any stimuli. Hydrocortisone severely depressed the production by these TCC of all the cytokines except for IL-2, which was slightly increased. Prostaglandin E2 depressed the production of IL-1 alpha, while it up-regulated the production of IL-6, TNF-alpha, and IFN-gamma. Rapamycin depressed the production of IL-6 and TNF-alpha, and FK506 depressed the production of TNF-alpha. Hydrocortisone also severely depressed the cytokine production by PHA-stimulated peripheral blood mononuclear cells obtained from healthy volunteers. Of the immunosuppressive agents tested, hydrocortisone exhibited the strongest suppression of cytokine production by HTLV-I-infected TCC. This result was in agreement with the in vivo effects of hydrocortisone in patients with HTLV-I uveitis. These TCC will be useful in investigating the effects of potential therapeutic agents for HTLV-I uveitis in vitro.