IMMUNE DEVELOPMENT IN YOUNG-ADULT C.RF-HYT MICE IS AFFECTED BY CONGENITAL AND MATERNAL HYPOTHYROIDISM

C.RF-hyt mice carry a mutation (hyt) that results in the phenotypic ex pression of congenital hypothyroidism in hyt/hyt mice due to a nonresp onsiveness of the thyroid gland to thyroid stimulating hormone. Hetero zygotes of this strain are euthyroid. To further define thyroid-immune interactions, the effect of congenital hypothyroidism and maternal hy pothyroidism 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 im mune development in these mice was compared on the basis of immune org an weights and the proliferation response of splenocytes stimulated wi th the T cell mitogens concanavalin A (Con A) and phytohemagglutinin a nd the B cell mitogen lipopolysaccharide. In addition, analysis of T c ell 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 revea led 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) increa se in the ratio between CD4(+) and CD8(+) splenocytes in hypothyroid c ompared with euthyroid mice. Data analyses for the main effects of mat ernal hypothyroidism revealed a significantly higher absolute (P = 0.0 25) 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 l ipopolysaccharides (P < 0.001) response, a marginally (P = 0.069) lowe r Con A to phytohemagglutinin response ratio, a lower (P = 0.001) perc entage of CD4(+) splenocytes, and a lower (P = 0.003) ratio between CD 4(+) and CD8(+) splenocytes in progeny of hypothyroid compared with pr ogeny of euthyroid mothers. These data provide further evidence for th e importance of normal thyroid function in the development, maintenanc e, and function of the immune system. It was concluded that not only c ongenital hypothyroidism results in altered immune development in youn g-adult mice, but also long-term effects on immune development occur i n progeny of hypothyroid mothers.