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Myocardial ischemia and reperfusion leads to transient CD8 immune deficiency and accelerated immunosenescence in CMV-seropositive patients

J. Hoffmann, EV. Shmeleva, SE. Boag, K. Fiser, A. Bagnall, S. Murali, I. Dimmick, H. Pircher, C. Martin-Ruiz, M. Egred, B. Keavney, T. von Zglinicki, R. Das, S. Todryk, I. Spyridopoulos,

. 2015 ; 116 (1) : 87-98.

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc15014007

RATIONALE: There is mounting evidence of a higher incidence of coronary heart disease in cytomegalovirus-seropositive individuals. OBJECTIVE: The aim of this study was to investigate whether acute myocardial infarction triggers an inflammatory T-cell response that might lead to accelerated immunosenescence in cytomegalovirus-seropositive patients. METHODS AND RESULTS: Thirty-four patients with acute myocardial infarction undergoing primary percutaneous coronary intervention were longitudinally studied within 3 months after reperfusion (Cohort A). In addition, 54 patients with acute myocardial infarction and chronic myocardial infarction were analyzed in a cross-sectional study (Cohort B). Cytomegalovirus-seropositive patients demonstrated a greater fall in the concentration of terminally differentiated CD8 effector memory T cells (TEMRA) in peripheral blood during the first 30 minutes of reperfusion compared with cytomegalovirus-seronegative patients (-192 versus -63 cells/μL; P=0.008), correlating with the expression of programmed cell death-1 before primary percutaneous coronary intervention (r=0.8; P=0.0002). A significant proportion of TEMRA cells remained depleted for ≥3 months in cytomegalovirus-seropositive patients. Using high-throughput 13-parameter flow cytometry and human leukocyte antigen class I cytomegalovirus-specific dextramers, we confirmed an acute and persistent depletion of terminally differentiated TEMRA and cytomegalovirus-specific CD8(+) cells in cytomegalovirus-seropositive patients. Long-term reconstitution of the TEMRA pool in chronic cytomegalovirus-seropositive postmyocardial infarction patients was associated with signs of terminal differentiation including an increase in killer cell lectin-like receptor subfamily G member 1 and shorter telomere length in CD8(+) T cells (2225 versus 3397 bp; P<0.001). CONCLUSIONS: Myocardial ischemia and reperfusion in cytomegalovirus-seropositive patients undergoing primary percutaneous coronary intervention leads to acute loss of antigen-specific, terminally differentiated CD8 T cells, possibly through programmed cell death-1-dependent programmed cell death. Our results suggest that acute myocardial infarction and reperfusion accelerate immunosenescence in cytomegalovirus-seropositive patients.

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$a Hoffmann, Jedrzej $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
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$a Myocardial ischemia and reperfusion leads to transient CD8 immune deficiency and accelerated immunosenescence in CMV-seropositive patients / $c J. Hoffmann, EV. Shmeleva, SE. Boag, K. Fiser, A. Bagnall, S. Murali, I. Dimmick, H. Pircher, C. Martin-Ruiz, M. Egred, B. Keavney, T. von Zglinicki, R. Das, S. Todryk, I. Spyridopoulos,
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$a RATIONALE: There is mounting evidence of a higher incidence of coronary heart disease in cytomegalovirus-seropositive individuals. OBJECTIVE: The aim of this study was to investigate whether acute myocardial infarction triggers an inflammatory T-cell response that might lead to accelerated immunosenescence in cytomegalovirus-seropositive patients. METHODS AND RESULTS: Thirty-four patients with acute myocardial infarction undergoing primary percutaneous coronary intervention were longitudinally studied within 3 months after reperfusion (Cohort A). In addition, 54 patients with acute myocardial infarction and chronic myocardial infarction were analyzed in a cross-sectional study (Cohort B). Cytomegalovirus-seropositive patients demonstrated a greater fall in the concentration of terminally differentiated CD8 effector memory T cells (TEMRA) in peripheral blood during the first 30 minutes of reperfusion compared with cytomegalovirus-seronegative patients (-192 versus -63 cells/μL; P=0.008), correlating with the expression of programmed cell death-1 before primary percutaneous coronary intervention (r=0.8; P=0.0002). A significant proportion of TEMRA cells remained depleted for ≥3 months in cytomegalovirus-seropositive patients. Using high-throughput 13-parameter flow cytometry and human leukocyte antigen class I cytomegalovirus-specific dextramers, we confirmed an acute and persistent depletion of terminally differentiated TEMRA and cytomegalovirus-specific CD8(+) cells in cytomegalovirus-seropositive patients. Long-term reconstitution of the TEMRA pool in chronic cytomegalovirus-seropositive postmyocardial infarction patients was associated with signs of terminal differentiation including an increase in killer cell lectin-like receptor subfamily G member 1 and shorter telomere length in CD8(+) T cells (2225 versus 3397 bp; P<0.001). CONCLUSIONS: Myocardial ischemia and reperfusion in cytomegalovirus-seropositive patients undergoing primary percutaneous coronary intervention leads to acute loss of antigen-specific, terminally differentiated CD8 T cells, possibly through programmed cell death-1-dependent programmed cell death. Our results suggest that acute myocardial infarction and reperfusion accelerate immunosenescence in cytomegalovirus-seropositive patients.
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$a Shmeleva, Evgeniya V $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
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$a Boag, Stephen E $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
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$a Fiser, Karel $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
700    1_
$a Bagnall, Alan $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
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$a Murali, Santosh $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
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$a Dimmick, Ian $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
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$a Pircher, Hanspeter $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
700    1_
$a Martin-Ruiz, Carmen $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
700    1_
$a Egred, Mohaned $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
700    1_
$a Keavney, Bernard $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
700    1_
$a von Zglinicki, Thomas $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
700    1_
$a Das, Rajiv $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
700    1_
$a Todryk, Stephen $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.).
700    1_
$a Spyridopoulos, Ioakim $u From the Institute of Genetic Medicine (J.H., E.V.S., S.E.B., S.M., B.K., I.S.), Institute of Aging and Health (C.M.-R., T.v.Z.), and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., S.T.), Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom (A.B., M.E., R.D., I.S.); Flow Cytometry Core Facility, International Center for Life, Newcastle upon Tyne, United Kingdom (I.D.); Department of Immunology, Institute of Medical Microbiology and Hygiene, Freiburg University, Germany (H.P.); CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic (K.F.); University Hospital Motol, Prague, Czech Republic (K.F.); Institute of Cardiovascular Sciences, The University of Manchester, United Kingdom (B.K.); and Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (S.M., S.T.). ioakim.spyridopoulos@newcastle.ac.uk.
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