Different in vitro proliferation and cytokine-production inhibition of memory T-cell subsets after calcineurin and mammalian target of rapamycin inhibitors treatment

Abstract

Calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORi) are the main immunosuppressants used for long-term maintenance therapy in transplant recipients to avoid acute rejection episodes. Both groups of immunosuppressants have wide effects and are focused against the T cells, although different impacts on specific T-cell subsets, such as regulatory T cells, have been demonstrated. A greater knowledge of the impact of immunosuppression on the cellular components involved in allograft rejection could facilitate decisions for individualized immunosuppression when an acute rejection event is suspected. Memory T cells have recently gained focus because they might induce a more potent response compared with naive cells. The impact of immunosuppressants on different memory T-cell subsets remains unclear. In the present study, we have studied the specific impact of CNI (tacrolimus) and mTORi (rapamycin and everolimus) over memory and naive CD4 + T cells. To do so, we have analysed the proliferation, phenotypic changes and cytokine synthesis in vitro in the presence of these immunosuppressants. The present work shows a more potent effect of CNI on proliferation and cytokine production in naive and memory T cells. However, the mTORi permit the differentiation of naive T cells to the memory phenotype and allow the production of interleukin-2. Taken together, our data show evidence to support the combined use of CNI and mTORi in transplant immunosuppression.