title: A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy.
abstract: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy.
authors.affiliation: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3875 Holman Street, Houston, Texas 77204, USA.|School of Kinesiology, Louisiana State University, Baton Rouge, LA 70802, United States.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Spielmann
authors.affiliation: Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington D.C., USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.affiliation: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3875 Holman Street, Houston, Texas 77204, USA.
authors.forename: Hawley
authors.initials: H
authors.lastname: Kunz
authors.affiliation: Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington D.C., USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanley
authors.affiliation: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3875 Holman Street, Houston, Texas 77204, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Simpson
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D003587:Cytomegalovirus / Q000276:immunology* / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D020031:Epstein-Barr Virus Infections / Q000517:prevention & control; D015444:Exercise / Q000502:physiology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D010750:Phosphoproteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014019:Tissue Donors; D015534:Trans-Activators / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D010750:Phosphoproteins; C090236:SM protein, Human herpesvirus 4; D015534:Trans-Activators; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa