Effects of Sirolimus treatment on patients with β-Thalassemia: Lymphocyte immunophenotype and biological activity of memory CD4+ and CD8+ T cells

Inhibitors of the mammalian target of rapamycin (mTOR) have been proposed to improve vaccine responses, especially in the elderly. Accordingly, testing mTOR inhibitors (such as Sirolimus) and other geroprotective drugs might be considered a key strategy to improve overall health resilience of aged populations. In this respect, Sirolimus (also known as rapamycin) is of great interest, in consideration of the fact that it is extensively used in routine therapy and in clinical studies for the treatment of several diseases. Recently, Sirolimus has been considered in laboratory and clinical studies aimed to find novel protocols for the therapy of hemoglobinopathies (e.g. beta-Thalassemia). The objective of the present study was to analyse the activity of CD4(+) and CD8(+) T cells in beta-Thalassemia patients treated with Sirolimus, taking advantages from the availability of cellular samples of the NCT03877809 clinical trial. The approach was to verify IFN-gamma releases following stimulation of peripheral blood mononuclear cells (PBMCs) to stimulatory CEF and CEFTA peptide pools, stimulatory for CD4(+) and CD8(+) T cells, respectively. The main results of the present study are that treatment of beta-Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4(+) and CD8(+) T cells releasing IFN-gamma following stimulation with antigenic stimuli present in immunological memory. These data are to our knowledge novel and in our opinion of interest, in consideration of the fact that beta-Thalassemia patients are considered prone to immune deficiency.

Automated summary

Inhibitors of mTOR, such as Sirolimus, can enhance vaccine responses in the elderly. Testing Sirolimus and other geroprotective drugs might be a key strategy to improve the overall health resilience of aged populations. This study analyzed the activity of CD4(+) and CD8(+) T cells in beta-Thalassemia patients treated with Sirolimus and found that it positively impacted the biological activity and number of memory T cells.