Heavy metal modulation of lymphocyte activities: I. In vitro effects of heavy metals on primary humoral immune responses

Abstract

The ability of heavy metals to modulate in vitro primary humoral immune responses has been investigated. The relative immunosuppresive activities of the heavy metals tested were Hg 2+ > Cu 2+ > Mn 2+ > Co 2+; Cd 2+ > Cr 3+; Sn 2+; Zn 2+. Fe 2+ had no significant effect on the development of SRBC-specific plaque-forming cells (PFC), and Pb 2+ and Ni 2+ enhanced the PFC response. The immunosuppressive activities of the heavy metals usually correlated with their toxicity and their inhibition of lymphocyte proliferation. The immunopotentiating metals, Pb 2+ and Ni 2+, alone induced lymphocyte proliferation, and they increased the proliferative response induced by LPS and 2-ME but not Con A and PHA. Although Pb 2+ and Ni 2+ were the only two heavy metals tested which enhanced lymphocyte reactivity, they did not appear to function via similar mechanisms. Pb 2+ appeared to enhance the development of PFC by directly interacting with lymphocytes and altering their activity since lymphocyte preincubation with Pb 2+ was sufficient for enhancement; whereas, lymphocyte preincubations with Ni 2+ did not induce enhancement. Pb 2+ did not appear to alter the immunogenicity of the antigens employed; however, pretreatment of SRBC with Ni 2+ eliminated their ability to stimulate a SRBC-specific response in vitro. Inhibition of the PFC response by the chelator EGTA could be reversed by Ca 2+ or Ni 2+, but not by Cu 2+, Hg 2+, Pb 2+, or Zn 2+. The stimulatory activity of Pb 2+ and Ni 2+ could not be accounted for by significant alteration of the antigenicity of the lymphocytes, because heavy metal preincubated syngeneic cells were not stimulatory for untreated syngeneic cells. On the other hand, Pb 2+ and Ni 2+ did slightly enhance the mixed lymphocyte culture (MLC) response to allogeneic cells; Hg 2+ inhibited the MLC response.