Iron Deficiency Alters the Progression of Mitogen-Treated Murine Splenic Lymphocytes through the Cell Cycle

Abstract

The influence of iron deficiency on the progression of mitogen-treated splenic lymphocytes through the cell cycle was studied in 16 control, 16 pair-fed, 15 iron-deficient (ID) and 16 ID mice that were repleted for up to 3 d (R3). The test and control diets differed only in iron concentrations (0.09 vs. 0.9 mmol/kg). When mice were killed (68 d of feeding), the hemoglobin concentration and liver iron stores of ID and R3 mice were <50% those of control mice (P < 0.05). Iron deficiency did not reduce the percentage of CD3(+) cells, but decreased CD3(+) cells/mg spleen (P < 0.05). In concanavalin A-treated and nonactivated cultures, there were no significant differences among groups in the percentages of cells in resting phase of the cell cycle (G0) to cell cycle initiation phase (G1), DNA synthesis phase (S) and exit from the S phase (G2) to mitosis phase (M) phases. In anti-CD3 and anti-CD3/anti-CD28-treated cultures, higher percentages of lymphocytes from ID and R3 mice than those from control and pair-fed mice were in the G0--G1 phase (P < 0.05). Conversely, lower percentages of activated cells from ID and R mice than those from control and pair-fed mice were in S and G2--M phases (P < 0.05). Incubation of lymphocytes with mitogens decreased the percentages of cells in G0--G1 phase from 90% to 80% in control and pair-fed but not in ID and R3 mice (P < 0.05). In activated cells, indices of iron status negatively correlated with the percentages of cells in G0--G1 (r = -0.306 to -0.597) but positively with those in S (r = 0.166--0.511) and G2--M phases (r = 0.265-0.59; P < 0.05). Data suggest that altered cell cycle progression likely contributes to impaired lymphocyte proliferation usually associated with iron deficiency.