Peripheral lymphocytes and intracellular cytokines in C282Y homozygous hemochromatosis patients.
OBJECTIVE
Several abnormalities in the immune status of hereditary hemochromatosis patients have been reported. We evaluated the peripheral blood lymphocytes phenotype and cytokine profile of CD8(+) and CD4(+) T cells in C282Y homozygous hereditary hemochromatosis patients compared to control subjects.


METHODS
Peripheral blood lymphocytes from 17 asymptomatic patients and 14 control subjects were analyzed. We determined the distribution of lymphocyte subsets and investigated at single-cell level by flow-cytometry the potential of cytokines production. The frequency of cytokine (interferon gamma, tumor necrosis factor alpha, interleukin 2 (IL-2), IL-4, IL-5, IL-10 and IL-13) producing cells was assessed in total T-lymphocytes, CD3(+)CD8(+) and CD3(+)CD4(+) subsets.


RESULTS
The patients studied showed a significant decrease of total lymphocyte count, T CD4(+)CD3(+), CD28(+), CD8(+)CD28(+) lymphocytes and natural killer (NK) CD56(+)CD16(+)CD3(-) cells. The reduction of CD28(+) and CD8(+)CD28(+) lymphocyte count was inversely related to transferrin saturation index. An increase in the ability of T-cells to produce all the cytokines studied and a major increase in IL-4 and IL-10 production in the CD3(+)CD8(+) subset was found. Our results demonstrate that activated Th1 and Th2 lymphocytes coexist in the peripheral blood of hereditary hemochromatosis patients and that T-cytotoxic (Tc) 2 subset is more expanded than in control population.


CONCLUSIONS
The association of a decreased number of T CD8(+) cytotoxic lymphocytes and NK cells, and the development of Tc2 cells in asymptomatic C282Y homozygous patients represents an imbalance in their immune function that might contribute to the high incidence of hepatocarcinoma.
Fabio
Giovanna
G
Department of Internal Medicine, University of Milan, Pad. Granelli, Via F. Sforza 35, 20122 Milan, Italy. giovanna.fabio@unimi.it
Zarantonello
Marina
M
Mocellin
Cristina
C
Bonara
Paola
P
Corengia
Chiara
C
Fargion
Silvia
S
Fiorelli
Gemino
G
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D014168:Transferrin / Q000032:analysis
D015703:Antigens, CD; D016207:Cytokines; D014168:Transferrin