Intrauterine Growth Restriction Alters T-Lymphocyte Cell Number and Dual Specificity Phosphatase 1 Levels in the Thymus of Newborn and Juvenile Rats

Abstract

Intrauterine growth restricted (IUGR) infants have increased susceptibility to infection associated with higher risk of illness and death. Dual specificity phosphatase 1 (DUSP1), which is transcribed in the thymus, increases in quantity as T cells mature and differentiate into CD4ϩ cells. Little is known about how IUGR affects DUSP1 levels and T-cell subpopulations over time. We hypothesized that IUGR would decrease cell count, CD4ϩ and CD8ϩ subpopulations of T lymphocytes, and DUSP1 levels in IUGR rat thymus and spleen. Bilateral uterine artery ligation produced IUGR rats. Thymus and spleen were harvested at P0 and P21. Flow cytometry was used to compare CD4ϩ and CD8ϩ lymphocyte populations. Real-time RT-PCR and Western blotting were used to determine DUSP1 quantity. IUGR significantly decreased total cell count in P0 and P21 IUGR male and female thymus. IUGR significantly increased CD4ϩ cells in IUGR P0 males and females, significantly decreased CD4ϩ cells in P21 female thymus, and significantly altered DUSP1 levels in the IUGR female thymus at P0 and P21, although it is not yet known whether the change in DUSP1 levels is due to a change in the level per cell or to a change in cellular composition of the thymus. (Pediatr Res 70: 123-129, 2011)

Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets

“…Lower cytokine expression per gram tissue could be explained by the presence of a lower total number of immune cells per tissue section. Research has reported that IUGR could reduce the total number of CD4 + and CD8 + T lymphocytes in the thymus (Contreras et al 2011). Similar findings were also observed in our study: Both the gene expression of CD4 and CD8 were reduced in the jejunum and ileum of IUGR neonatal piglets (unpublished data).…”

“…IUGR also alters T lymphocyte cell numbers and impairs cellular immunity in neonates (Contreras et al 2011;Zhong et al 2012). Previous studies have demonstrated that IUGR impairs the development of the small intestine (SI), damages the SI structure, and changes the bacterial colonization of the intestine (Wang et al 2005;D'Inca et al 2010a).…”

Impaired intestinal mucosal immunity is associated with the imbalance of T lymphocyte sub-populations in intrauterine growth-restricted neonatal piglets

“…A previous study also reported that the percentage of CD4 + CD8 + T lymphocytes of the total cells in the thymus of IUGR neonates on day 1 was lower than that in NBW piglets, but no significant difference in the CD4 + T lymphocyte number between NBW and IUGR piglets was observed (Lin et al, 2009). Research on newborn IUGR rats has reported that IUGR significantly decreases the total cell and CD4 + cell counts in the thymus (Contreras et al, 2011). Another study reported that IUGR increased the CD8 + T cell count in the thymus of young rats (Jenkins et al, 2006), which was in accordance with our study.…”

Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep

“…Reduced nutrient availability in utero might directly reduce cell proliferation in immune tissues. Thymus weight was reduced in IUGR humans (7,11) and newborn PR rats, and the spleen and thymus of PR rats had fewer lymphocytes at weaning (6). In adolescent humans, circulating concentrations of thymopoietin, a hormone produced by the thymus that regulates T-cell differentiation and function, were lower in SGA than adequate size for gestational age individuals who had been exclusively breast-fed for at least 50 days after birth (17).…”