Differential effects of iron status on lymphocyte subsets in lupus and non-lupus strains of mice

Abstract

The MRL/MPJ-lpr/lpr (MRL) mouse is a model of human systemic lupus erythematosus (SLE) and develops autoimmunity accompanied by lymphadenopathy and accumulation of cells bearing CD3+L3T4-Lyt2-markers. Since iron status was previously shown to alter disease manifestation in these mice, the effect of iron status on lymphocyte subsets was studied. Weanling female MRL mice were divided into four groups (n=9–10) and fed purified diets containing varying levels of iron: 4 mg/kg diet-severely deficient (SD); 35 mg/kg diet-iron-adequate controls (C); and 250 mg/kg diet-iron supplemented (IS). A fourth group was fed C diet in amounts eaten by the SD group-pair-fed controls (PF). C3H/Hej (C3H) mice were fed the same diets and served as non-SLE controls. At 18 weeks of age, both MRL and C3H SD mice were anemic; however, MRL SD mice were significantly more anemic as reflected in lower hemoglobin and hematocrit levels. Spleen and lymph node weights were lowest in MRL SD and PF mice, and spleen cell number was significantly reduced in SD mice. Iron deficiency in C3H mice resulted in reduced percentages of total T lymphocytes, T helper/inducer and T suppressor/cytotoxic, and B lymphocytes. The T helper/T suppressor cell ratio was not affected. The percentage of B cells was also reduced in C3H IS mice compared to C mice. In MRL mice, iron status had no effect on the percentages of T cells, T helper cells, or B cells, nor the estimated percentage of cells expressing the double negative (CD3+L3T4-Lyt 2-) phenotype. T supressor/cytotoxic cells were significantly higher in the lymph nodes of SD MRL mice. No statistical differences were found in the T helper/T suppressor ratio. This study has demonstrated differential effects of iron status on lymphocyte subsets of SLE and non-SLE strains of mice. Altered disease manifestation by iron status in MRL-lpr mice is not related to reductions in T and B lymphocytes or the CD3+L3T4- Lyt 2-population