The effect of iron on the MLR was examined by pretreating peripheral blood mononuclear cells from 77 unrelated Caucasians with five concentrations of Ferric-citrate (10.0 mM, 1.0 mM, 0.1 mM, 0.01 mM and 0.005 mM). After incubation with the metal, the cells were washed and cultured in a one-way MLR with a pool of stimulator cells. Cell viability remained unchanged (greater than 90 percent) during the 6-day culture period. Citrate per se had no effect on either the responder or the stimulator population. Iron treatment influenced the MLR in the following ways: (1) a variable degree of inhibition was observed which related to the dose of Ferric-citrate used and to HLA phenotype, (2) the responder but not the stimulator cells were affected, (3) no statistically significant differences were seen between female and male donor cells and (4) the mean percent response of cells from HLA-A2 donors were significantly (0.005<P<0.01) less susceptible to iron exposure than those from non-HLA-A2 individuals. The present results indicate that iron can interact with lymphoid cells and influence some immunological functions in vitro. The possibility is discussed that similar interactions take place in vivo which could contribute to the prognosis of certain diseases associated with particular HLA phenotypes.
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