Clonal analysis of the effect of iron on human cytotoxic and proliferating T lymphocytes.
The immunoregulatory effect of non-transferrin-bound iron (Fe3+) on the proliferative and cytotoxic responses of normal human T lymphocytes was studied using a sensitive limit-dilution technique capable of detecting the responses of individual lymphocytes. Iron, present in the form of ferric citrate at concentrations from 0.03 to 1.0 mmol/L, significantly reduced the cloning frequency of peripheral blood T lymphocytes. The effect of iron appeared, however, to be targeted to individual clones in that some clones that did grow in the presence of iron achieved a normal rate of proliferation. Thus, iron was not non-specifically toxic. At these same concentrations ferric citrate also produced significant reductions in the cloning frequency of CD4+ CD8-precursor T lymphocytes. Reductions in the response of T lymphocyte precursors capable of cytotoxic activity occurred in the presence of ferric citrate from 0.1 to 1.0 mmol/L. These data support the hypothesis that non-transferrin-bound iron has an immunoregulatory role in cell-mediated immunity.
Rudd
M J
MJ
Department of Medicine, University of Queensland, Royal Brisbane Hospital, Australia.
Good
M F
MF
Chapman
D E
DE
Powell
L W
LW
Halliday
J W
JW
D000911:Antibodies, Monoclonal; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D002999:Clone Cells / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; 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
D000911:Antibodies, Monoclonal; D002951:Citrates; D019343:Citric Acid