Effect of transferrin, lactoferrin and chelated iron on human T-lymphocytes

The effect of different forms of iron and iron-binding proteins on the proliferative response of human lymphocytes to phytohaemagglutinin (PHA) has been studied. Transferrin enhanced proliferation, the effect being proportional to the degree of iron saturation up to 100%, but decreased if additional iron was present. The lipophilic complex ferric pyridoxal isonicotinoyl hydrazone (FePIH) also enhanced proliferation, but the hydrophilic complex ferric nitrilotriacetate (FeNTA) was inhibitory. Fe-lactoferrin could not substitute for Fe-transferrin, although iron-free (apo) lactoferrin abrogated the inhibitory effect seen when iron levels exceed the binding capacity of transferrin. Lymphocyte ferritin levels increased 4-fold as the iron saturation of transferrin increased from 0 to 90% but no further increase was seen at higher iron levels, suggesting that lymphocytes are poorly equipped to detoxify excess iron through stimulation of ferritin synthesis. The effect of iron on the CD4:CD8 ratio after 72 h culture with PHA was also examined. The ratio was approximately 2:1 for cells cultured with transferrin at iron saturations between 0 and 75%, with FePIH, or without either, but decreased to 1.1:1 when cells were cultured in the presence of FeNTA, regardless of whether or not saturated Fe-transferrin was present. These results show that iron can affect lymphocyte proliferation and subset ratios in different ways according to the form and amount present, and may help to explain some of the immunological disturbances associated with iron overload.