- Email: [email protected]
174. Early life adversity, depressive symptoms, and endothelial dysfunction in women veterans
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Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
Evidence suggests a cause and effect relationship between inflammatory cytokines and behavioral symptoms relevant to a number of psychiatric illnesses. Previous neuroimaging studies have demonstrated that administration of inflammatory stimuli or cytokines changes activity of basal ganglia nuclei to mediate depressive symptoms, effects that may be mediated by decreased striatal dopamine. Whether the effects of inflammation extend beyond the basal ganglia to other brain regions to contribute to specific behavioral symptoms is unknown. This study examined whether increased inflammation in depression affects functional connectivity between the basal ganglia (striatum) and other brain regions to mediate depressive and neurocognitive symptoms. Wakeful resting-state fMRI pilot data were obtained from 17 currently depressed patients with low versus high inflammation (C-reactive protein 6 3 versus >3 mg/L). Seed-to-whole brain correlations were computed and compared between groups using four predefined striatal seeds. Depressed patients with high inflammation exhibited attenuated functional connectivity between three striatal seeds and thirteen cortical or subcortical brain regions. Of these thirteen significant relationships, inflammation-related compromised connectivity between ventral striatum and both anterior cingulate cortex and amygdala correlated with symptoms of anhedonia and anxiety, whereas decreased connectivity between dorsal striatum and prefrontal cortex was associated with decreased psychomotor performance. Understanding inflammation-associated alterations in neurocircuitry that mediate specific depressive behaviors is important for identifying strategies to diagnose and treat behavioral symptoms in patients with increased inflammation. http://dx.doi.org/10.1016/j.bbi.2014.06.191
172. Early life stress and perinatal glucocorticoid exposure produce complex immune system alterations, including accelerated T cell immunosenescence, in adolescent rhesus macaques J.N. Kohn a,b, B.R. Howell a, D.B. Guzman a,b, J.S. Meyer c, C.C. Ibegbu d, M.M. Sanchez a,e a
Yerkes National Primate Research Center, Division of Developmental and Cognitive Neuroscience, 954 Gatewood Rd., Atlanta, GA 30329, USA b Emory University, Graduate Program in Neuroscience, USA c Dept of Psychology, University of Massachusetts, Amherst, MA, USA d Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA e Dept of Psychiatry and Behavioral Sciences, Emory University, School of Medicine, Atlanta, GA 30322, USA Early life stress, including childhood maltreatment, has deleterious, persistent effects on immune function that increase disease morbidity and mortality across the lifespan. Evidence suggests that excess glucocorticoid (GC) exposure, whether during gestation or through childhood trauma, may mediate immune system dysregulation; however, the relative contribution of prenatal and postnatal GCs to immune dysregulation, and whether they interact, remains unclear. To address this question, we cross-fostered infants from maltreating (MT; n = 20) and non-maltreating (CON; n = 20) rhesus macaque mothers and immunophenotyped blood leukocytes from their adolescent offspring for cellular activation, proliferation, and senescence. To compare the contribution of prenatal vs. postnatal GC exposure, hair cortisol was assayed at 2 days and 6 months post-birth. We found that compared to individuals reared by CON dams, postnatal cortisol levels from MT infants were elevated by 22% (p = 0.03) and predicted lower adolescent CD4:CD8 ratios (p = 0.043), but were not affected by prenatal cortisol levels. Biological mother (CON vs. MT) significantly predicted naive:memory CD4 + T cell ratios in adolescence (p = 0.045), irrespective of prenatal or postnatal cortisol, or of foster mother. However, MT animals had
increased monocyte proportions (p = 0.019), irrespective of cortisol or biological mother. T cell activation and proliferation were unaffected by maltreatment or cortisol. These findings indicate that specific immunological phenotypes are differentially affected by prenatal and postnatal experience, including maltreatment and GC exposure. http://dx.doi.org/10.1016/j.bbi.2014.06.192
173. Weight dissatisfaction is associated with low-grade inflammation and self-reported chronic stress for women but not men A.M. Geiger a, M. Wing a, K.M. Rene b, N.J. Sabik a, J.M. Wolf a a Brandeis University, Psychology, 415 South St., Brown 125 MS 062, Waltham, MA 02453, USA b Tufts University Medical Center, USA
Previous research on dissatisfaction with body weight has focused primarily on psychological consequences and the relationship to disordered eating behaviors in females. The present study aimed at examining sex differences in the role of negative feelings about weight on psychological as well as physiological health outcomes. Participants were 25 female and 14 male college students (age: 20.46 ± 2.32 years) with average BMI of 23.22 ± 3.8. Participants self-reported perceived chronic stress and weight-specific body esteem. As a physiological health marker, CRP levels were assessed in dried blood spots. While no sex differences were found for BMI, females had higher CRP levels (t = 2.14, p = .04) and lower weight body esteem (t = 2.30, p = .03). Controlling for BMI, women with higher weight dissatisfaction reported more stress while for men, stress levels were independent from feelings about weight (beta = .37, p = .04). While women with more negative feelings about weight had higher CRP levels than those with higher body esteem, there was no relationship for men (beta = .35, p = .066). Findings support the idea that low body esteem, specifically weight dissatisfaction, may be a chronic stressor for females. Weight dissatisfaction was further linked to chronic low-grade inflammation, thus suggesting a mechanism linking current weight concerns to future negative health outcomes. Weight concerns did not contribute to chronic stress or inflammation in men. This may suggest gender differences in the role of body esteem in the development of stress-related disease. http://dx.doi.org/10.1016/j.bbi.2014.06.193
174. Early life adversity, depressive symptoms, and endothelial dysfunction in women veterans K.L. Saban a,c, H.L. Mathews a, E. Collins b, L.W. Janusek a a
Loyola University Chicago, Maywood, IL 60153, USA University of Illinois Chicago, USA c Edward Hines Jr. Veterans Administration, USA b
Veterans are at particular risk for cardiovascular disease (CVD) and this may be related to early life adversity. Prior research demonstrates early life adversity promotes inflammation, which contributes to not only depressive symptoms but also to endothelial dysfunction, a precursor to CVD. Compared to female civilians, women Veterans have greater histories of abuse and therefore may be at particular risk for CVD. The purpose of this pilot study was to evaluate early life adversity, depressive symptoms, and endothelial dysfunction in women Veterans. A cross sectional sample of women Veterans (mean age = 50.47) completed the Childhood Trauma Questionnaire (CTQ) and the Center for Epidemiologic Stud-
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
ies Depression Scale (CES-D). Endothelial function was assessed by measurement of flow-mediated vasodilation using the Peripheral Arterial Tone (PAT) signaling technology, which non-invasively measures arterial tone in peripheral arterial beds. Subjects reported high levels of depressive symptoms that were positively associated with CTQ early life adversity subscales of emotional neglect (r = .669, p = .003), physical neglect (r = .590, p = .013), emotional abuse (r = .768, p = .000), and physical abuse (r = .537, p = .026). Nearly one third of the subjects (29.3%) had demonstrable endothelial dysfunction with Reactive Hyperemia Index (RHI) scores <1.67. These results demonstrate women Veterans to be at particular risk for CVD due to an increased incidence of early life adversity, depressive symptomatology and endothelial dysfunction. http://dx.doi.org/10.1016/j.bbi.2014.06.194
175. High levels of aerobic fitness are associated with fewer senescent T-cells and a lower prevalence of latent cytomegalovirus infection in healthy men N.H. Agha, A.B. Bigley, G. Spielmann, E.C. LaVoy, M. Pistillo, H.E. Kunz, M. Hussain, R.J. Simpson University of Houston, Health and Human Performance, 3855 Holman St. Rm 104 Garrison, Houston, TX 77204-6015, USA The immune risk profile (IRP) is an array of immunological biomarkers that is associated with decreased vaccine efficacy, increased disease susceptibility and 3–5 year mortality in the elderly. Increased proportions of KLRG1 + CD28-CD8 (senescent) T-cells and latent cytomegalovirus (CMV) infection are key components of the IRP. We have previously shown that high aerobic fitness levels (determined by VO2 max) are associated with a decreased accumulation of senescent T-cells during aging, but it is not known if fitness affects CMV prevalence or viral load. T-cell phenotypes and CMV status was determined in 74 healthy men (aged 18–64) categorized as ‘‘High Fit’’ (n = 36) or ‘‘Low Fit’’ (n = 38) according to age-adjusted VO2max scores. High aerobic fitness was associated with lower proportions of senescent CD8+ T-cells (23.0% v 46.6%; p < 0.05) and lower CMV seroprevalence (33.3% v 63.2%), but did not impact CMV IgG antibody titers (a measure of viral load) in the seropositive participants. Although CMV can drive T-cell differentiation, the effects of fitness on senescent CD8+ T-cell proportions withstood adjustment for CMV serostatus, indicating that fitness may impact the composition of the CD8+ T-cell pool independently of CMV. Plasma testosterone levels and serostatus/titers for Epstein-Barr virus, toxoplasmosis, and Helicobacter Pylori were not affected by fitness. In conclusion, high levels of aerobic fitness across the lifespan are associated with a less differentiated T-cell profile and a lower prevalence of CMV. http://dx.doi.org/10.1016/j.bbi.2014.06.195
176. Immune cell phenotypes and NK-cell function in astronauts and controls 5 months before a 6-month mission to the International Space Station G. Spielmann a, A.B. Bigley a, B.E. Crucian b, S. Mehta a, D. Pierson a, H. Kunz a, N. Agha a, E.C. LaVoy a, R.J. Simpson a a
Laboratory of Integrated Physiology, Department of Health and Human Performance, 3855 Holman Street, University of Houston, Houston, TX 77204, USA b NASA – Johnson Space Center, Houston, TX, USA
e51
Human space exploration provides great technological, medical and academic advances to humanity, but also poses many threats to the health of the crew. Astronauts are subjected to a myriad of both physical and psychological stressors that may negatively affect the immune system and increase the risk of an adverse health event in flight. In this ongoing study, we compared immune cell phenotypes and NK-cell activity (NKCA) between astronauts and controls 5-months before a 6-month mission to the International Space Station (ISS). Blood samples were taken from 6 astronauts and 6 nonastronaut controls and assayed for immune cell phenotypes and NKCA by flow cytometry. Astronauts had lower proportions and numbers of naïve KLRG1 /CD28+ (p < 0.05) and CD45RA+/CD62L+ (p < 0.05) CD4+ and CD8+ T-cells, and higher numbers of memory KLRG1+/CD28+ (p < 0.05) CD8+ T-cells than controls. NKCA against the K562 (leukemia origin) and 721.221 (lymphoma origin) target cells tended to be higher in astronauts compared to controls but this was not statistically significant (p = 0.089 and p = 0.081 respectively). NKCA against the U266 (myeloma origin) target cell did not differ between astronauts and controls (p > 0.05). We conclude that astronauts display only small baseline differences in T-cell phenotype and NKCA compared to controls when assessed 5-months prior to launch. This study will continue to monitor immune function changes in these astronauts and ground-based controls during and after a 6-month mission to the ISS. http://dx.doi.org/10.1016/j.bbi.2014.06.196
177. A single bout of exercise augments the expansion of multi-virus specific T-cells in healthy humans R.J. Simpson a, G. Spielmann a, P. Hanley b, C.M. Bollard b a
Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, TX 77204, USA b Children’s National Medical Center, Washington, DC, USA 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 virusspecific 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 virusreacting 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. http://dx.doi.org/10.1016/j.bbi.2014.06.197
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
Evidence suggests a cause and effect relationship between inflammatory cytokines and behavioral symptoms relevant to a number of psychiatric illnesses. Previous neuroimaging studies have demonstrated that administration of inflammatory stimuli or cytokines changes activity of basal ganglia nuclei to mediate depressive symptoms, effects that may be mediated by decreased striatal dopamine. Whether the effects of inflammation extend beyond the basal ganglia to other brain regions to contribute to specific behavioral symptoms is unknown. This study examined whether increased inflammation in depression affects functional connectivity between the basal ganglia (striatum) and other brain regions to mediate depressive and neurocognitive symptoms. Wakeful resting-state fMRI pilot data were obtained from 17 currently depressed patients with low versus high inflammation (C-reactive protein 6 3 versus >3 mg/L). Seed-to-whole brain correlations were computed and compared between groups using four predefined striatal seeds. Depressed patients with high inflammation exhibited attenuated functional connectivity between three striatal seeds and thirteen cortical or subcortical brain regions. Of these thirteen significant relationships, inflammation-related compromised connectivity between ventral striatum and both anterior cingulate cortex and amygdala correlated with symptoms of anhedonia and anxiety, whereas decreased connectivity between dorsal striatum and prefrontal cortex was associated with decreased psychomotor performance. Understanding inflammation-associated alterations in neurocircuitry that mediate specific depressive behaviors is important for identifying strategies to diagnose and treat behavioral symptoms in patients with increased inflammation. http://dx.doi.org/10.1016/j.bbi.2014.06.191
172. Early life stress and perinatal glucocorticoid exposure produce complex immune system alterations, including accelerated T cell immunosenescence, in adolescent rhesus macaques J.N. Kohn a,b, B.R. Howell a, D.B. Guzman a,b, J.S. Meyer c, C.C. Ibegbu d, M.M. Sanchez a,e a
Yerkes National Primate Research Center, Division of Developmental and Cognitive Neuroscience, 954 Gatewood Rd., Atlanta, GA 30329, USA b Emory University, Graduate Program in Neuroscience, USA c Dept of Psychology, University of Massachusetts, Amherst, MA, USA d Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA e Dept of Psychiatry and Behavioral Sciences, Emory University, School of Medicine, Atlanta, GA 30322, USA Early life stress, including childhood maltreatment, has deleterious, persistent effects on immune function that increase disease morbidity and mortality across the lifespan. Evidence suggests that excess glucocorticoid (GC) exposure, whether during gestation or through childhood trauma, may mediate immune system dysregulation; however, the relative contribution of prenatal and postnatal GCs to immune dysregulation, and whether they interact, remains unclear. To address this question, we cross-fostered infants from maltreating (MT; n = 20) and non-maltreating (CON; n = 20) rhesus macaque mothers and immunophenotyped blood leukocytes from their adolescent offspring for cellular activation, proliferation, and senescence. To compare the contribution of prenatal vs. postnatal GC exposure, hair cortisol was assayed at 2 days and 6 months post-birth. We found that compared to individuals reared by CON dams, postnatal cortisol levels from MT infants were elevated by 22% (p = 0.03) and predicted lower adolescent CD4:CD8 ratios (p = 0.043), but were not affected by prenatal cortisol levels. Biological mother (CON vs. MT) significantly predicted naive:memory CD4 + T cell ratios in adolescence (p = 0.045), irrespective of prenatal or postnatal cortisol, or of foster mother. However, MT animals had
increased monocyte proportions (p = 0.019), irrespective of cortisol or biological mother. T cell activation and proliferation were unaffected by maltreatment or cortisol. These findings indicate that specific immunological phenotypes are differentially affected by prenatal and postnatal experience, including maltreatment and GC exposure. http://dx.doi.org/10.1016/j.bbi.2014.06.192
173. Weight dissatisfaction is associated with low-grade inflammation and self-reported chronic stress for women but not men A.M. Geiger a, M. Wing a, K.M. Rene b, N.J. Sabik a, J.M. Wolf a a Brandeis University, Psychology, 415 South St., Brown 125 MS 062, Waltham, MA 02453, USA b Tufts University Medical Center, USA
Previous research on dissatisfaction with body weight has focused primarily on psychological consequences and the relationship to disordered eating behaviors in females. The present study aimed at examining sex differences in the role of negative feelings about weight on psychological as well as physiological health outcomes. Participants were 25 female and 14 male college students (age: 20.46 ± 2.32 years) with average BMI of 23.22 ± 3.8. Participants self-reported perceived chronic stress and weight-specific body esteem. As a physiological health marker, CRP levels were assessed in dried blood spots. While no sex differences were found for BMI, females had higher CRP levels (t = 2.14, p = .04) and lower weight body esteem (t = 2.30, p = .03). Controlling for BMI, women with higher weight dissatisfaction reported more stress while for men, stress levels were independent from feelings about weight (beta = .37, p = .04). While women with more negative feelings about weight had higher CRP levels than those with higher body esteem, there was no relationship for men (beta = .35, p = .066). Findings support the idea that low body esteem, specifically weight dissatisfaction, may be a chronic stressor for females. Weight dissatisfaction was further linked to chronic low-grade inflammation, thus suggesting a mechanism linking current weight concerns to future negative health outcomes. Weight concerns did not contribute to chronic stress or inflammation in men. This may suggest gender differences in the role of body esteem in the development of stress-related disease. http://dx.doi.org/10.1016/j.bbi.2014.06.193
174. Early life adversity, depressive symptoms, and endothelial dysfunction in women veterans K.L. Saban a,c, H.L. Mathews a, E. Collins b, L.W. Janusek a a
Loyola University Chicago, Maywood, IL 60153, USA University of Illinois Chicago, USA c Edward Hines Jr. Veterans Administration, USA b
Veterans are at particular risk for cardiovascular disease (CVD) and this may be related to early life adversity. Prior research demonstrates early life adversity promotes inflammation, which contributes to not only depressive symptoms but also to endothelial dysfunction, a precursor to CVD. Compared to female civilians, women Veterans have greater histories of abuse and therefore may be at particular risk for CVD. The purpose of this pilot study was to evaluate early life adversity, depressive symptoms, and endothelial dysfunction in women Veterans. A cross sectional sample of women Veterans (mean age = 50.47) completed the Childhood Trauma Questionnaire (CTQ) and the Center for Epidemiologic Stud-
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
ies Depression Scale (CES-D). Endothelial function was assessed by measurement of flow-mediated vasodilation using the Peripheral Arterial Tone (PAT) signaling technology, which non-invasively measures arterial tone in peripheral arterial beds. Subjects reported high levels of depressive symptoms that were positively associated with CTQ early life adversity subscales of emotional neglect (r = .669, p = .003), physical neglect (r = .590, p = .013), emotional abuse (r = .768, p = .000), and physical abuse (r = .537, p = .026). Nearly one third of the subjects (29.3%) had demonstrable endothelial dysfunction with Reactive Hyperemia Index (RHI) scores <1.67. These results demonstrate women Veterans to be at particular risk for CVD due to an increased incidence of early life adversity, depressive symptomatology and endothelial dysfunction. http://dx.doi.org/10.1016/j.bbi.2014.06.194
175. High levels of aerobic fitness are associated with fewer senescent T-cells and a lower prevalence of latent cytomegalovirus infection in healthy men N.H. Agha, A.B. Bigley, G. Spielmann, E.C. LaVoy, M. Pistillo, H.E. Kunz, M. Hussain, R.J. Simpson University of Houston, Health and Human Performance, 3855 Holman St. Rm 104 Garrison, Houston, TX 77204-6015, USA The immune risk profile (IRP) is an array of immunological biomarkers that is associated with decreased vaccine efficacy, increased disease susceptibility and 3–5 year mortality in the elderly. Increased proportions of KLRG1 + CD28-CD8 (senescent) T-cells and latent cytomegalovirus (CMV) infection are key components of the IRP. We have previously shown that high aerobic fitness levels (determined by VO2 max) are associated with a decreased accumulation of senescent T-cells during aging, but it is not known if fitness affects CMV prevalence or viral load. T-cell phenotypes and CMV status was determined in 74 healthy men (aged 18–64) categorized as ‘‘High Fit’’ (n = 36) or ‘‘Low Fit’’ (n = 38) according to age-adjusted VO2max scores. High aerobic fitness was associated with lower proportions of senescent CD8+ T-cells (23.0% v 46.6%; p < 0.05) and lower CMV seroprevalence (33.3% v 63.2%), but did not impact CMV IgG antibody titers (a measure of viral load) in the seropositive participants. Although CMV can drive T-cell differentiation, the effects of fitness on senescent CD8+ T-cell proportions withstood adjustment for CMV serostatus, indicating that fitness may impact the composition of the CD8+ T-cell pool independently of CMV. Plasma testosterone levels and serostatus/titers for Epstein-Barr virus, toxoplasmosis, and Helicobacter Pylori were not affected by fitness. In conclusion, high levels of aerobic fitness across the lifespan are associated with a less differentiated T-cell profile and a lower prevalence of CMV. http://dx.doi.org/10.1016/j.bbi.2014.06.195
176. Immune cell phenotypes and NK-cell function in astronauts and controls 5 months before a 6-month mission to the International Space Station G. Spielmann a, A.B. Bigley a, B.E. Crucian b, S. Mehta a, D. Pierson a, H. Kunz a, N. Agha a, E.C. LaVoy a, R.J. Simpson a a
Laboratory of Integrated Physiology, Department of Health and Human Performance, 3855 Holman Street, University of Houston, Houston, TX 77204, USA b NASA – Johnson Space Center, Houston, TX, USA
e51
Human space exploration provides great technological, medical and academic advances to humanity, but also poses many threats to the health of the crew. Astronauts are subjected to a myriad of both physical and psychological stressors that may negatively affect the immune system and increase the risk of an adverse health event in flight. In this ongoing study, we compared immune cell phenotypes and NK-cell activity (NKCA) between astronauts and controls 5-months before a 6-month mission to the International Space Station (ISS). Blood samples were taken from 6 astronauts and 6 nonastronaut controls and assayed for immune cell phenotypes and NKCA by flow cytometry. Astronauts had lower proportions and numbers of naïve KLRG1 /CD28+ (p < 0.05) and CD45RA+/CD62L+ (p < 0.05) CD4+ and CD8+ T-cells, and higher numbers of memory KLRG1+/CD28+ (p < 0.05) CD8+ T-cells than controls. NKCA against the K562 (leukemia origin) and 721.221 (lymphoma origin) target cells tended to be higher in astronauts compared to controls but this was not statistically significant (p = 0.089 and p = 0.081 respectively). NKCA against the U266 (myeloma origin) target cell did not differ between astronauts and controls (p > 0.05). We conclude that astronauts display only small baseline differences in T-cell phenotype and NKCA compared to controls when assessed 5-months prior to launch. This study will continue to monitor immune function changes in these astronauts and ground-based controls during and after a 6-month mission to the ISS. http://dx.doi.org/10.1016/j.bbi.2014.06.196
177. A single bout of exercise augments the expansion of multi-virus specific T-cells in healthy humans R.J. Simpson a, G. Spielmann a, P. Hanley b, C.M. Bollard b a
Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, TX 77204, USA b Children’s National Medical Center, Washington, DC, USA 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 virusspecific 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 virusreacting 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. http://dx.doi.org/10.1016/j.bbi.2014.06.197