Thymic Atrophy during Infection as a Host Response to Avoid Tolerance to Persistent Pathogens

Abstract

The immune system consists in part of a functionally competent T -cell repertoire that is reactive to foreign antigens but tolerant to self -antigens. The repertoire of T cells is primarily formed in the thymusthrough positive and negative selection of developing thymocytes that are critical for establishing central tolerance. One of the features of the thymus is to sense stress hormones produced in pathophysiological conditions. Increased levels of these hormones are associated with infections and are able to induce thymic atrophy. We have shown that in acuteTrypanosoma cruziinfections, the atrophic thymus is a consequence of increased thymocyte apoptosis and premature export of immature thymocytes to secondary lymph nodes. Thisatrophy does not necessarily result in dysfunction of the thymus since the organ micro architecture is preserved and maintains negative selection, thus avoiding the development of tolerance to the pathogen during the establishment of protective immunity. However, in chronic infections, the dissemination of invading pathogens able to target the thymus i