Abstract
Iron, an essential growth trace element, is required for proliferation of all living cells, including T lymphocytes. Many, though not all, immune responses require lymphocyte proliferation. Iron deficiency, a worldwide public health problem for children and for women of childbearing age, is associated with impaired lymphocyte proliferative responses to mitogens and cell‐mediated immunity. However, the mechanisms have not been fully elucidated. Our data on certain early key events in the T cell activation pathways, obtained from iron‐deficient murine splenic T lymphocytes, show reductions in hydrolysis of cell membrane phosphatidyl inositol 4,5 bisphosphate, protein kinase C activation, and interleukin‐2 secretion. Although the expression of CD3 molecule (a component of the T cell‐receptor/CD3 complex, required for T cell activation) is not decreased by iron deficiency in splenocytes and thymocytes, the expression of the co‐stimulatory molecule, CD28, is. Iron‐deficiency increases the percentage of CD3+/CD28− thymocytes but decreases that of CD3−/CD28+ cells. Iron deficiency and iron chelation by deferoxamine decrease CD28 fluorescence intensity but tends to increase that of CD3. Progression of activated spleen cells through the cell cycle (Go/G1, S, G2/M phases) is also altered by iron deficiency independently of differences in the percentages of CD3+ T cells between groups, probably through impaired transition of G1 to S phase. Data suggest that the role of iron in T cell proliferation is not limited to the regulation of ribonucleotide reductase activity, but also involves other steps in the T cell activation pathways. J. Trace Elem. Exp. Med. 16:219–225, 2003. © 2003 Wiley‐Liss, Inc.