Environmental endocrine disruptors and amphibian immunity: A bridge between the thyroid hormone axis and T cell development.

Immunity is susceptible to reprogramming by environmental chemical and endocrine signals. Notably, numerous thyroid disrupting chemicals (TDCs) have the potential to perturb immune endpoints, but data are lacking on the mechanisms by which TDCs can influence the development of the immune system. T cell immunity is particularly vulnerable to modulation by TDCs during thymic education, differentiation, and selection. The following review discusses the ways in which thyroid hormones may influence T cell development, as well as emerging TDCs with potential to impact both thyroid hormone physiology and immune outcomes. To overcome the challenges of studying TDC impacts on immune toxicological endpoints, a comparative approach using the amphibian Xenopus laevis is recommended. X. laevis are ideally suited to studying TDC impacts on immunity due to the importance of thyroid hormones for metamorphosis, and the wealth of immunological models to measure immune endpoints in both tadpoles and adult frogs.

Developmental exposure to thyroid disrupting chemical mixtures alters metamorphosis and post-metamorphic thymocyte differentiation.

While there is some evidence to suggest that disruption of the thyroid hormone (TH)-axis during perinatal development may weaken T cell immunity later in life, data are currently lacking on whether environmentally relevant thyroid disrupting chemicals (TDCs) can induce similar outcomes. To fill this gap in knowledge, X. laevis tadpoles were exposed to an environmentally relevant mixture of TDCs, either during early tadpole development, or immediately before and during metamorphosis, to assess T cell differentiation and anti-viral immune response against FV3 infection after metamorphosis. Extending our previous study showing a delay in metamorphosis completion, here we report that TDC exposure prior to metamorphosis reduced the frequency of surface MHC-II + splenic lymphocytes and weakened some aspects of the anti-viral immune response. TDC exposure during metamorphosis slowed post-metamorphic migration of the thymus reduced the renewal of cortical thymocytes and splenic CD8 + T cells. The results indicate that TDC exposure during perinatal development may perturb the formation of T cell immunity later in life.