FK-506 inhibits proliferation and IL-4 messenger RNA production by a T-helper 2 cell line.
FK-506 is a potent immunosuppressant which is known to decrease the generation of allospecific cytotoxic T cells, possibly through its effect on cytokine production. FK-506 has been reported to have a suppressive effect on cytokine synthesis and secretion by pooled lymphocytes; its action on more selective subsets of lymphocytes is unknown. We currently report the effect of FK-506 on proliferation and IL-4 messenger RNA production by the differentiated mouse T-helper 2 cell line Ly1+2-/9. Ly1+2-/9 cells were grown in culture and treated with (1) media alone, (2) Con A, (3) FK-506, and (4) Con A + FK-506. Proliferation to Con A was determined by treating cells with 10 micrograms/ml Con A +/- FK-506 and measuring [3H]TdR uptake. Reverse transcriptase-polymerase chain reaction amplification was used to quantitate the level of IL-4 mRNA expression. FK-506 markedly inhibits Con A-induced proliferation and IL-4 mRNA production by the T-helper 2 cell line Ly1+2-/9. The ability of FK-506 to block the proliferation and IL-4 production by this helper cell subset suggests that this effect may contribute to its observed marked immunosuppressive properties in vitro and in vivo.
Wang
S C
SC
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania.
Jordan
M L
ML
Tweardy
D J
DJ
Wright
J
J
Hoffman
R A
RA
Simmons
R L
RL
D002455:Cell Division; D002460:Cell Line; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology*
D012333:RNA, Messenger; D015847:Interleukin-4; D016559:Tacrolimus