Leukotriene C4 (LTC4) produced by a human T-T hybridoma suppresses pokeweed mitogen (PWM) induced immunoglobulin (Ig) production by human mononuclear cells

Human T lymphocytes are capable of secreting many different lymphokines which regulate Ig production. The authors produced a human T-T fusion between T cells from a normal donor and the T lymphoma line CEM-6. From this fusion 3 of 180 clones produced a factor which suppressed polyclonal Ig production by PWM-stimulated mononuclear cells. All 3 clones expressed both T4 and T8 surface markers; CEM-6 is T4+/T8+. Suppression of Ig production did not involve cytotoxicity and was most effective when the hybridoma supernatant was added during the first 3 d of culture. Production of the suppressive factor could be inhibited by corticosteroids but not indomethacin. Analysis of the hybridoma supernatant by reverse phase chromatography revealed a peak of suppressive activity in the fraction where purified LTC4 could be eluted. Crude hybridoma supernatant contained 10-50 ng/ml of LTC4, but no LTB4 by radioimmunoassay (RIA). In addition, LTC4 produced by the hybridomas co-eluted with purified LTC4 as assessed by RIA. No LTC4 was found in nonsuppressive hybridoma supernatants. Furthermore, antibody to LTC4 could absorb suppressive activity from hybridoma supernatants. Thus, human T lymphocytes produce LTC4 which suppresses polyclonal Ig production by human mononuclear cells