Neonatal exposure to propylthiouracil induces a shift in lymphoid cell sub-populations in the developing postnatal male rat spleen and thymus

Abstract

Evidence of the connections between the immune system and the thyroid axis is increasingly strong; however, much of the data are focused on immune effects of altered thyroid status in adults or rodents with congenital defects of the pituitary/thyroid axis. The object of the present study was to determine the effects of PTU-induced hypothyroidism on the developing immune system of the rat by focussing on both the spleen and thymus gland. Male Sprague–Dawley rat pups were exposed to PTU through maternal milk by giving the mothers 0.02% PTU in their drinking water starting on the pups’ day of birth until day 24 (d24), shortly before weaning on d28. Animals were sampled on days 14, 22, 30, and 91. The mean body weight was decreased in the PTU-treated animals on days 14, 22, and 30. The mean spleen and thymic weights and cellularity were all decreased in the PTU-treated animals on d22 and d30. PTU exposure increased the proportion of NK cells in the spleen on days 14, 22, and 30. The proportion of T-cells was increased on days 22 and 30 with a particular increase in the CD4+ T-cells, resulting in an increase in the ratio of helper T-cells to suppressor/cytotoxic T-cells at d22. PTU also decreased the proportion of splenic B-cells at days 14, 22, and 30 which could explain the increased proportion of both NK and T-cells during these sampling periods. PTU treatment decreased the lytic ability of NK cells at d22, but no functional differences were observed at days 14, 30, 91, despite the increased proportion of NK cells in PTU-exposed animals at days 14, 22, and 30. PTU exposure also increased the proportion of CD4+CD8− cells in the thymus on d22 and caused an increase in both the CD4+CD8− and CD4−CD8+ populations on d30. These data suggest that the effects of temporary, PTU-induced hypothyroidism on the cell populations in the spleen partially result from transient changes in thymic T-cell development, including a shift towards increased CD4+CD8− cells. The data also suggest that temporary hypothyroidism early in development decreases B-cell development in a transient fashion. Temporary hypothyroidism induced from birth to the latter stages of the weaning period induced transitory effects on the spleen, thymus, and immune cell sub-populations—all of which recovered to normal values when the animals matured.