Iron, iron-binding proteins and immune system cells.

In summary, the work reviewed in the present paper indicates that 1. Iron and the iron-binding proteins can act as regulators of immune function, and not only as a result of a nutritional dependence of lymphoid cells on transferrin and transferrin-iron. Subsets of cells of the immune system respond differently to increases in iron concentration in vitro and in vivo. 2. Macrophages and lymphocytes differ in the H and L subunit content of the ferritins synthesized in response to increases in iron concentration in vitro. 3. NK activity by adherent and nonadherent cells differ in their susceptibility to the enhancing effect of lactoferrin in vitro. 4. Responses to mitogen stimulation by PHA and Con A are diminished, while the PWM response remains unaffected by exposure to acidic ferritins or by increasing concentrations of iron in vitro and in vivo. 5. Pretreatment of effector but not target cells with iron results in diminished responses in the MLR, an effect that appears to be related to the HLA-A locus. 6. In situ hybridization studies indicate that transferrin is synthesized by a specific subset of the T lymphocytes. 7. Transient increases in serum iron concentration above the full saturation of transferrin, reproducing the clinical situation frequently seen in hereditary hemochromatosis, are followed by a series of cellular changes in the synovium that can be correlated to changes in the course of an experimental model of arthritis in the rat.