RAPAMYCIN INDUCES TRANSFORMING GROWTH FACTOR-?? PRODUCTION BY LYMPHOCYTES1

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Abstract
Background. Under certain conditions rapamycin and transforming growth factor- (TGF) β have similar immunoregulatory effects, suggesting a potential functional link between rapamycin and TGF-β. Methods. Splenic leukocytes were stimulated in vitro with anti-CD3 or with allogeneic cells in vivo in the presence or absence of rapamycin. TGF-β production by activated lymphocytes was quantitated using ELISA. Results. Splenic leukocytes from BALB/c mice that were primed with allogeneic cells and conditioned with rapamycin in vivo as well as splenic leukocytes that were treated with rapamycin in vitro produced significantly higher levels of TGF-β upon anti-CD3 stimulation as compared with untreated controls. Conclusion. Our data suggest that rapamycin can program activated lymphocytes to produce TGF-β. Thus, the immunosuppressive effects of rapamycin may be partially mediated by TGF-β.