The effect of non-transferrin-bound iron on murine T lymphocyte subsets: analysis by clonal techniques.
A number of different immunological properties have been attributed to iron (Fe3+ and Fe2+) and iron-binding proteins. However, in many previous studies, high concentrations of iron were used and cell-cell interactions were not excluded as a possible cause of the observed immunomodulatory effects. In this study, clonal techniques have been used to examine the effect of non-transferrin-bound iron (Fe3+) on the T lymphocyte subsets required for the generation of cytotoxic T lymphocytes (CTL). Concentrations of non-transferrin-bound Fe3+ of 10 microM or greater were shown to inhibit the generation of C57, BALB/c and CBA allo-specific CTL in bulk culture. Limit-dilution analysis revealed that: (i) Fe3+ reduced the cloning efficiency of CTL-precursors (CTL-P) by up to 96% without affecting the rate of clone growth; (ii) Fe3+ did not affect the cloning efficiency of allo-stimulated Ly-2-ve T cell precursors but reduced the rate of clone growth of these cells; (iii) Fe3+ enhanced, by more than 13-fold, the function of clones of Concanavalin A (Con A)-induced suppressor T lymphocytes (STL) which suppressed in vitro the development of CTL from their precursor cells. The data provide further evidence that low concentrations of non-transferrin-bound Fe3+, of the same order as those reported to be present in the serum of patients with iron-overload, have significant immunoregulatory properties.
D000818:Animals; D002999:Clone Cells / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005290:Ferric Compounds / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D005290:Ferric Compounds; C025314:ferric citrate