Prevention of thymus involution rescues old mice from fatal Toxoplasma gondii infection

Abstract Thymic epithelial cells (TEC) make up the thymic microenvironments that support the generation of a functionally competent and self-tolerant T-cell repertoire. Infections, starvation, and aging, among other factors, cause thymus involution with loss of T-cell generation and decreased frequency of naive T-cells in secondary lymphoid organs. However, the causes and consequences of thymus involution are not clearly understood. Since thymus function declines with involution, we need a better understanding how the thymus controls T cell development. We found that constitutive overexpression of Myc (cMycTg) in TEC prevents thymus involution, causing a dramatic increase in thymus size in adult mice (Cowan et al, 2019). In addition, cMycTg mice restored frequencies of CD4+ and CD8+ naive T-cell populations to the levels observed in young adult mice. In unpublished work, we have found that prevention of thymus involution rescues aging mice from lethal Toxoplasma gondii infection. During the acute infection, old mice showed a significantly decreased frequency of parasite-specific T-cells and increased serum levels of IFNγ, IL6 and TNFα. Furthermore, antibody depletion of T-cells in aging mice challenged with Toxoplasma gondii prolonged their survival. These findings identify a role for thymic involution in the age-associated mortality of Toxoplasma gondii infection. We are now investigating the mechanisms responsible for the pathogenic immune responses seen in aged individuals to understand how improved thymic function modifies immune responses. AMS is supported by the patronage of the Children’s Hospital of Mexico. SCS, JEC and AB are supported by the NIH Intramural Cancer Research Training Award to post-doctoral fellows.