The effect of metallothionein (MT) on lymphocytes was studied in vitro. Rab
bit MT induced the proliferative responses of mouse splenocytes at concentr
ations of 1-25 mu g/ml. MT synergistically enhanced Con A- or LPS-induced p
roliferative response of splenocytes. A similar effect was also observed fo
r rabbit splenocytes at a similar concentration. Free heavy metals such as
Cd and Zn only weakly stimulated splenocytes. 2-mercaptoethanol (2-Me) abro
gated the effect of MT, suggesting that thiols in MT play an: important rol
e for splenocyte response. MT stimulated splenocytes from MT-knockout mice
as well as those from normal control mouse. The responder cells for MT stim
ulation were B cells and MT also induced B cell differentiation to produce
Ig. MT induced the calcium influx-of B cells, but not T cells. These result
s indicate that MT has a potent immunomodulating activity, especially on B
cells. (C) 2000 International Society for Immunopharmacology. Published by
Elsevier Science Ltd. All rights reserved.