Immune Development in Young-Adult C.RF-hyt Mice Is Affected by Congenital and Maternal Hypothyroidism

Abstract

Abstract

C.RF-hyt mice carry a mutation (hyt) that results in the phenotypic expression of congenital hypothyroidism in hyt/hyt mice due to a nonresponsiveness of the thyroid gland to thyroid-stimulating hormone. Heterozygotes of this strain are euthyroid. To further define thyroid-immune interactions, the effect of congenital hypothyroidism and maternal hypothyroidism on immune development were examined in 3- to 4-month-old hyt/+ and hyt/hyt progeny from hyt/+ and hyt/hyt dams.

The state of immune development in these mice was compared on the basis of immune organ weights and the proliferation response of splenocytes stimulated with the T cell mitogens concanavalin A (Con A) and phytohemagglutinin and the B cell mitogen lipopolysaccharide. In addition, analysis of T cell subpopulations in thymus and spleen was conducted using direct and indirect immunofluorescence and flow cytometry.

Data analyses for the main effects of congenital hypothyroidism on immune development revealed a significantly lower absolute thymus weight (P < 0.001), a lower (P = 0.022) percentage of thymocytes expressing CD8 (CD8+), a higher (P = 0.010) ratio between CD4+ and CD8+ thymocytes, a lower (P < 0.001) absolute and adjusted spleen weight, a lower (P = 0.001) Con A to phytohemagglutinin response ratio, a higher (P = 0.003) percentage of CD4+ splenocytes, and a marginally significant (P = 0.055) increase in the ratio between CD4+ and CD8+ splenocytes in hypothyroid compared with euthyroid mice.

Data analyses for the main effects of maternal hypothyroidism revealed a significantly higher absolute (P = 0.025) and adjusted (P = 0.001) thymus weight, a higher (P = 0.006) ratio between CD4+ and CD8+ thymocytes, a lower Con A (P = 0.018) and lipopolysaccharides (P < 0.001) response, a marginally (P = 0.069) lower Con A to phytohemagglutinin response ratio, a lower (P = 0.001) percentage of CD4+ splenocytes, and a lower (P = 0.003) ratio between CD4+ and CD8+ splenocytes in progeny of hypothyroid compared with progeny of euthyroid mothers.

These data provide further evidence for the importance of normal thyroid function in the development, maintenance, and function of the immune system. It was concluded that not only congenital hypothyroidism results in altered immune development in young-adult mice, but also long-term effects on immune development occur in progeny of hypothyroid mothers.