Enhancement of Antiviral T-Cell Responses by Vitamin C Suggests New Strategies to Improve Manufacturing of Virus-Specific T Cells for Adoptive Immunotherapy

SIMPLE SUMMARY: Leukemia and lymphoma patients are routinely transplanted with hematopoietic stem cells. Due to the required immunosuppression, bacterial, viral and fungal infections are life-threatening complications after transplantation. In recent years, treatment with virus-specific T cells isolated from stem cell, family or third-party donors has emerged as an alternative to conventional therapies. Since vitamins are described to influence the immune system and its cellular components, the aim of this study was to examine whether vitamins modulate virus-specific T-cell function and thereby enable an improvement of therapy. We were able to show that vitamin C increases the expansion and activation state of virus-specific T cells, and an increased influence of vitamin C was observed on cells isolated from male donors and donors above 40 years of age. In conclusion, this study provides insights into the impact of vitamin C on virus-specific T cells, thereby suggesting its potential application as additional selection criteria and a strategy to improve virus-specific T-cell therapy. ABSTRACT: Allogeneic and autologous transplantation of hematopoietic stem cells (HSCT) are being routinely used to treat patients with leukemia and lymphoma. Due to the required immunosuppression after stem cell transplantation, infection and reactivation by viruses are life-threatening complications. In recent years, adoptive transfer using virus-specific T cells (VSTs) has emerged as alternative to conventional therapies. Since vitamins are described to influence the immune system and its cellular components, the aim of this study was to examine whether vitamins modulate VST function and thereby enable an improvement of therapy. For that, we investigated the impact of vitamin C and D on the functionality of cytomegalovirus (CMV)-specific T cells isolated from CMV-seropositive healthy donors. We were able to show that vitamin C increases the expansion and activation state of CMV-specific T cells, and an increased influence of vitamin C was observed on cells isolated from male donors and donors above 40 years of age. A higher frequency of the terminally differentiated effector memory CD8(+) T-cell population in these donors indicates a connection between these cells and the enhanced response to vitamin C. Thus, here we provide insights into the impact of vitamin C on cytotoxic T cells as well as possible additional selection criteria and strategies to improve VST functionality.