Thymic rejuvenation with GHS tesamorelin in a “dirty” mouse model

Abstract

Age-related thymic involution is one of the major reasons behind compromised adaptive immune responses in the elderly. It is characterized by the progressive reduction in thymic mass, accumulation of adipose tissue within the thymus, and disruption of unique thymic structure, which results in impaired T cell development and reduced naïve T cell output with age. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) treatments have shown promise in restoring the functionality of the aged thymus albeit with unwanted side effects. While GH secretagogue (GHS) ghrelin has thymus-rejuvenating effects, the effects of a similar GHS called tesamorelin have not yet been studied. Since tesamorelin stimulates endogenous GH production similar to ghrelin and has fewer metabolic side effects than exogenous GH treatment, we hypothesize that it could have positive effects on thymus functioning and T cell development. In this study, the effects of tesamorelin on T cell populations in the thymus, as well as secondary lymphoid organs, were investigated using the “dirty” mouse model that better resembles the human immune system than conventional SPF mice. We report that while tesamorelin does not have thymus-rejuvenating effects in the 6.5- month-old “dirty” mice, it does promote the accumulation of antigen-experienced memory T cell subsets and decrease of naïve T cell subsets in the murine spleen. Although further research is required, we suggest this splenic accumulation is the reflection of the decreased levels of activated cytotoxic T cell markers in the peripheral blood of HIV patients treated with clinical grade tesamorelin.