Young mice were found to have serum copper concentrations ranging from
a low of 0.291 to a high of 0.584 ppm. Old mice had serum copper conc
entrations ranging from 0.223 to 1.715 with 30.9% of the old animals h
aving values greater than 0.6 ppm. The mitogen response of isolated ly
mphocytes from the spleens of aging mice was greatly reduced when thes
e cells were taken from animals with naturally occurring serum copper
levels in excess of 0.6 ng of copper/mg wet weight serum. The lymphocy
tes taken from young mice with higher serum copper concentrations, on
the other hand, had increased response to mitogens. Addition of the co
pper protein, ceruloplasmin, to lymphocyte cultures in vitro reduced t
he mitogen response of purified splenic lymphocytes with the reduction
being greater for cells from old animals. We suggest that excess seru
m copper and ceruloplasmin may be immunosuppressive, especially in old
er organisms.