Lymphocyte Subsets in Experimental Hemochromatosis

Abstract

The distribution of lymphocyte subsets in blood, thymus, spleen, mesenteric lymph nodes, Peyer’s patches and bone marrow was evaluated in an experimental model of secondary hemochromatosis in rats. The values of CD2, CD4, CD 8, B and NK cells in these different lymphoid compartments did not differ between the control group and the experimental group. These results suggest that the abnormalities of lymphocyte subsets previously reported in patients with secondary hemochromatosis may be due to factors other than iron overload.

Total blood lymphocyte counts in hemochromatosis probands with HFEC282Y homozygosity: relationship to severity of iron overload and HLA-A and -B alleles and haplotypes

“…In sub-Saharan Africans with African iron overload, a disorder that is typically not linked to HLA or HFE C282Y, there was no significant association of serum ferritin concentrations and total blood lymphocyte counts [3,39]. In an experimental model of secondary iron overload in rats, the distribution of lymphocyte subsets in blood, thymus, spleen, mesenteric lymph nodes, Peyer patches, and bone marrow were similar in control and experimental groups [40]. Altogether, these results suggest that there is not a consistent relationship of severity of iron overload with CD4/CD8 ratios, blood T-lymphocyte subsets, or abnormal total blood lymphocyte counts in patients with hemochromatosis or in those with iron overload due to other causes [3,41].…”

Iron and Immunity: Immunological Consequences of Iron Deficiency and Overload

“…Some studies on patients with HFE -associated hemochromatosis indicate a decrease in circulating lymphocytes, with CD8+ cells being particularly affected (Barton et al 2005; Macedo et al 2010), but these abnormalities have not been observed consistently. Experimental iron overload in rodents is not associated with altered lymphocyte numbers, but has been suggested to affect proliferative and cytokine responses (Melo et al 1997; Mencacci et al 1997; Wu et al 1990). This is an area that would benefit from further research, especially in the context of the more recent developments in the iron metabolism field.…”

The novel SLC40A1 (T419I) variant results in a loss-of-function phenotype and may provide insights into the mechanism of large granular lymphocytic leukemia and pure red cell aplasia

“… 31 Rats loaded with iron by iron-dextran injection have been reported to harbor increased CD8 + T cells, although the relationship between iron overload and T lymphocytes remains controversial. 32 , 33 In humans, somatic gain-of-function variants in STAT3 were associated with LGLL and PRCA, and the activated STAT3 could induce the expression of hepcidin, leading to a decreased capacity of iron export by FPN, which was somehow similar to FD. 34 , 35 Notably, the mode of iron overload in FD is different from other hemochromatosis and T cells are not heavily dependent on iron as that of erythroid cells.…”

“…When activated, T cells intake more iron by increasing surface expression of transferrin receptor 1 31 . Rats loaded with iron by iron-dextran injection have been reported to harbor increased CD8 + T cells, although the relationship between iron overload and T lymphocytes remains controversial 32,33 . In humans, somatic gain-of-function variants in STAT3 were associated with LGLL and PRCA, and the activated STAT3 could induce the expression of hepcidin, leading to a decreased capacity of iron export by FPN, which was somehow similar to FD 34,35 .…”