期刊
JOURNAL OF IMMUNOTOXICOLOGY
卷 17, 期 1, 页码 135-143出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/1547691X.2020.1767238
关键词
Arsenic; prenatal; CD4+T cell; IL-2; immunosuppression
类别
资金
- ICMR-National Institute of Cholera and Enteric Diseases
Arsenic (As) readily crosses the placenta and exposure of the fetus may cause adverse consequences later in life, including immunomodulation. In the current study, the question was asked how the immune repertoire might respond in postnatal life when there is no further As exposure. Here, pregnant mice (Balb/c [H-2(d)]) were exposed to arsenic trioxide (As2O3) through their drinking water from time of conception until parturition. Their offspring, 4-week-old mice who had not been exposed again to As, were used for functional analyses of innate, humoral and cellular immunity. Compared to cells from non-As-exposed dam offspring, isolated peritoneal macro-phages (M phi) displayed no differences in T-cell stimulating ability. Levels of circulating IgG(2a)but not IgG(1)were decreased in As-exposed dam offspring as compared to control offspring counterparts. Mixed-leukocyte reactions (MLR) indicated that CD4(+)T-cells from the prenatal As-exposed mice were significantly less responsive to allogenic stimulation as evidenced by decreases in interferon (IFN)-gamma and IL-2 production and in expression of CD44 and CD69 (but not CD25) activation markers. Interestingly, the M phi from the prenatal As-exposed mice were capable of stimulating normal allogenic T-cells, indicating that T-cells from these mice were refractory to allogenic signals. There was also a significant decrease in absolute numbers of splenic CD4(+)and CD8(+)T-cells due to prenatal As exposure (as compared to control). Lastly, the impaired immune function of the prenatal As-exposed mice was correlated with a very strong susceptibility toEscherichia coliinfection. Taken together, the data from this study clearly show thatin uteroAs exposure may continue to perpetuate a dampening effect on the immune repertoire of offspring, even into the early stages of postnatal life.
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