177. A single bout of exercise augments the expansion of multi-virus specific T-cells in healthy humans

Abstract

Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The adoptive transfer of multi-virus specific cytotoxic T-cell lines (CTLs) expanded from a suitably matched donor can reproducibly control infections after HSCT. However, the failure to generate sufficient numbers of virus-specific CTLs ex vivo can often result in inadequate restoration of antiviral immunity and poor prognosis. Because exercise mobilizes large numbers of viral specific T-cells into the bloodstream, we hypothesized that a single bout of exercise would increase the expansion of multi-viral-specific CTLs in would be HSCT donors. Healthy CMV and EBV seropositive subjects performed 30-min of cycling exercise at +15% of the individual blood lactate threshold. A fixed number of PBMCs isolated before and immediately after exercise were pulsed with overlapping peptides spanning all target viral antigens and expanded with IL-4, IL-7 and IL-15 over 9-days. Exercise remarkably increased the expansion of cytomegalovirus (CMV) pp65 (∼3.8-fold), CMV IE-1 (∼4.7-fold) and Epstein-Barr virus (EBV) BMLF-1 (∼2.8-fold) specific CTLs over 9-days, although did not reliably increase the expansion of EBV LMP-2 specific CTLs. All virus-reacting cells were of a CD62L- memory phenotype and remained elevated after exercise even when adjusted for input T-cell numbers. We conclude that exercise may serve as a simple strategy to reliably augment the ex vivo expansion of viral-specific CTLs for adoptive transfer immunotherapy after HSCT.