Open AccessThe effects of β1 and β1+2 adrenergic receptor blockade on the exercise-induced mobilization and ex vivo expansion of virus-specific T cells: implications for cellular therapy and the anti-viral immune effects of exercise
Author(s) -
Hawley Kunz,
Nadia H. Agha,
Maryam Hussain,
Emily C. LaVoy,
Kyle A. Smith,
Preteesh Leo Mylabathula,
Douglass M. Diak,
Forrest L. Baker,
Daniel P. O’Connor,
Richard A. Bond,
Emmanuel Katsanis,
Catherine M. Bollard,
Richard J. Simpson
Publication year - 2020
Publication title -
cell stress and chaperones
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.994
H-Index - 87
eISSN - 1466-1268
pISSN - 1355-8145
DOI - 10.1007/s12192-020-01136-7
Subject(s) - nadolol , medicine , peripheral blood mononuclear cell , ex vivo , immunology , adoptive cell transfer , immune system , placebo , in vivo , endocrinology , pharmacology , t cell , chemistry , pathology , biology , in vitro , biochemistry , microbiology and biotechnology , propranolol , alternative medicine
The adoptive transfer of donor-derived virus-specific T cells (VSTs) is an effective treatment for infections following allogeneic hematopoietic cell transplantation. Acute exercise mobilizes effector lymphocytes and VSTs to the circulation and augments the ex vivo manufacture of VSTs. This study determined if β 2 adrenergic receptor (AR) signaling precipitated the VST response to acute exercise. Healthy participants (n = 12) completed 30 min of steady-state cycling exercise after ingesting a placebo, a β 1 + 2 AR antagonist (nadolol) or a β 1 AR antagonist (bisoprolol). Circulating VSTs to cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (AdV) antigens were enumerated before and after exercise, and peripheral blood mononuclear cells were cultured with viral peptides for 8 days to expand multi-VSTs. Compared with placebo, nadolol blunted the exercise-induced mobilization of CMV-VSTs (Δ VSTs/100,000 CD3 + T cells = 93 ± 104 vs. 22 ± 91 for placebo and nadolol, respectively; p = 0.036), while bisoprolol did not, despite both drugs evoking similar reductions in exercising heart rate and blood pressure. Circulating AdV and EBV VSTs (VSTs/mL blood) only increased after exercise with placebo. Although not significant, nadolol partially mitigated exercise-induced increases in multi-VST expansion, particularly in participants that demonstrated an exercise-induced increase in VST expansion. We conclude that exercise-induced enhancements in VST mobilization and expansion are at least partially β 2 AR mediated, thus highlighting a role for the β 2 AR in targeted therapy for the augmentation of VST immune cell therapeutics in the allogeneic adoptive transfer setting. Moreover, long-term regular exercise may provide additional viral protection in the host through frequent β 2 AR-dependent mobilization and redistribution of VSTs cumulated with each bout of exercise.