IN-VITRO IMMUNO-CYTOTOXICITY OF IRON EVALUATED BY DNA-SYNTHESIS OF HUMAN T-LYMPHOCYTES STIMULATED VIA CD2 AND CD3

In previous studies it was demonstrated that the in vitro exposure of human lymphocytes to iron, nickel or cobalt salts causes a significant reduction of lymphocytes expressing CD2 and CD3 surface antigens. Sin ce both molecules are involved in T lymphocyte activation, these studi es suggest that the above metals might affect T-cell activation and pr oliferation. Thus a method was developed for the stimulation of lympho cytes in which both CD2 and CD3 molecules were triggered simultaneousl y. For this purpose an anti-CD3 monoclonal antibody (mAb) was chemical ly bound to human erythrocytes (HE), forming HEalphaCD3 conjugates, wh ich were used for lymphocyte stimulation. In this work the effects of iron on lymphocyte proliferation was studied, following stimulation vi a CD2 and CD3, in order to evaluate the immuno-cytotoxicity of iron. I ncreasing concentrations (5 x 10(-3) muM-10(2) muM) of iron citrate (F e-citrate) showed that the higher concentration range (10 muM-10(2) mu M) caused moderate inhibitions of lymphocyte DNA synthesis (ranging be tween 18.3% and 78.6%). Furthermore the presence of monocytes in cultu re did not interfere in the inhibitory effect of Fe-citrate. Phenotypi c characterisation of DNA-synthesizing cells in the presence of Fe-cit rate showed that the CD8+ (suppressor/cytotoxic) subset was the most r educed one. This study showed that iron inhibited T lymphocyte prolife ration, particularly the suppressor/cytotoxic cells, suggesting that t he presence of high levels of iron in in vivo situations can cause imm unosuppression and, consequently, contribute to the onset of opportuni stic infections and tumours.