About this Journal Submit a Manuscript Table of Contents 
Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 347213, 9 pages
http://dx.doi.org/10.1155/2013/347213
Research Article

Clinical Factors Influencing Phenotype of HCMV-Specific CD8+ T Cells and HCMV-Induced Interferon-Gamma Production after Allogeneic Stem Cells Transplantation

Inmaculada Gayoso,1,2,3 Sara Cantisán,1,2,3 Carolina Cerrato,1,4 Joaquín Sánchez-García,1,4 Carmen Martin,1,4 Rafael Solana,1,3,5 Antonio Torres-Gomez,1,4 and Julian Torre-Cisneros1,2,3

1Instituto Maimonides para la Investigacion Biomedica de Córdoba (IMIBIC), Reina Sofia University Hospital, 14004 Cordoba, Spain
2Department of Infectious Diseases and IMIBIC, Reina Sofia University Hospital, Avenida Menéndez Pidal s/n, 14004 Cordoba, Spain
3Spanish Network for Research in Infectious Diseases (REIPI), IMIBIC, Reina Sofia University Hospital, Avenida Menéndez Pidal s/n, 14004 Cordoba, Spain
4Department of Haematology and IMIBIC, Reina Sofia University Hospital, Avenida Menéndez Pidal s/n, 14004 Cordoba, Spain
5Department of Immunology and IMIBIC, Reina Sofia University Hospital, Avenida Menéndez Pidal s/n, 14004 Cordoba, Spain

Received 25 June 2012; Revised 29 December 2012; Accepted 2 January 2013

Academic Editor: Hans Hellmut Hirsch

Copyright © 2013 Inmaculada Gayoso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. A. Barron, D. Gao, K. L. Springer et al., “Relationship of reconstituted adaptive and innate cytomegalovirus (CMV)-specific immune responses with CMV viremia in hematopoietic stem cell transplant recipients,” Clinical Infectious Diseases, vol. 49, no. 12, pp. 1777–1783, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. R. Seggewiss and H. Einsele, “Immune reconstitution after allogeneic transplantation and expanding options for immunomodulation: an update,” Blood, vol. 115, no. 19, pp. 3861–3868, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. J. A. Brown, K. Stevenson, H. T. Kim et al., “Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis,” Blood, vol. 115, no. 20, pp. 4111–4119, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. G. Avetisyan, K. Larsson, J. Aschan, C. Nilsson, M. Hassan, and P. Ljungman, “Impact on the cytomegalovirus (CMV) viral load by CMV-specific T-cell immunity in recipients of allogeneic stem cell transplantation,” Bone Marrow Transplantation, vol. 38, no. 10, pp. 687–692, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Boeckh, W. G. Nichols, G. Papanicolaou, R. Rubin, J. R. Wingard, and J. Zaia, “Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies,” Biology of Blood and Marrow Transplantation, vol. 9, no. 9, pp. 543–558, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. T. Bunde, A. Kirchner, B. Hoffmeister et al., “Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells,” Journal of Experimental Medicine, vol. 201, no. 7, pp. 1031–1036, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. S. Ganepola, C. Gentilini, U. Hilbers et al., “Patients at high risk for CMV infection and disease show delayed CD8+ T-cell immune recovery after allogeneic stem cell transplantation,” Bone Marrow Transplantation, vol. 39, no. 5, pp. 293–299, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. J. W. Gratama, M. Boeckh, R. Nakamura et al., “Immune monitoring with iTAg MHCTetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study,” Blood, vol. 116, no. 10, pp. 1655–1662, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Cwynarski, J. Ainsworth, M. Cobbold et al., “Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation,” Blood, vol. 97, no. 5, pp. 1232–1240, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Hakki, S. R. Riddell, J. Storek et al., “Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: Impact of host factors, drug therapy, and subclinical reactivation,” Blood, vol. 102, no. 8, pp. 3060–3067, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. E. Özdemir, L. S. St John, G. Gillespie et al., “Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells,” Blood, vol. 100, no. 10, pp. 3690–3697, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Romero, A. Zippelius, I. Kurth et al., “Four functionally distinct populations of human effector-memory CD8+ T lymphocytes,” Journal of Immunology, vol. 178, no. 7, pp. 4112–4119, 2007. View at Scopus
  13. N. Rufer, A. Zippelius, P. Batard et al., “Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions,” Blood, vol. 102, no. 5, pp. 1779–1787, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. V. Appay, P. R. Dunbar, M. Callan et al., “Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections,” Nature Medicine, vol. 8, no. 4, pp. 379–385, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. N. P. Weng, A. N. Akbar, and J. Goronzy, “CD28− T cells: their role in the age-associated decline of immune function,” Trends in Immunology, vol. 30, no. 7, pp. 306–312, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. A. N. Akbar and J. M. Fletcher, “Memory T cell homeostasis and senescence during aging,” Current Opinion in Immunology, vol. 17, no. 5, pp. 480–485, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Cantisán, J. Torre-Cisneros, R. Lara et al., “Age-dependent association between low frequency of CD27/CD28 expression on pp65 CD8+ T cells and cytomegalovirus replication after transplantation,” Clinical and Vaccine Immunology, vol. 16, no. 10, pp. 1429–1438, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. N. Khan, N. Shariff, M. Cobbold et al., “Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals,” Journal of Immunology, vol. 169, no. 4, pp. 1984–1992, 2002. View at Scopus
  19. G. Pawelec, A. Akbar, C. Caruso, B. Grubeck-Loebenstein, R. Solana, and A. Wikby, “Human immunosenescence: is it infectious?” Immunological Reviews, vol. 205, pp. 257–268, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. P. Scheinberg, J. J. Melenhorst, J. M. Brenchley et al., “The transfer of adaptive immunity to CMVduring hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor,” Blood, vol. 114, no. 24, pp. 5071–5080, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. M. L. Pita-Lopez, G. Inmaculada, O. DelaRosa, et al., “Effect of ageing on CMV-specific CD8 T cells from CMV seropositive healthy donors,” Immunity and Aging, vol. 6, article 11, 2009.
  22. X. H. Luo, X. J. Huang, K. Y. Liu, L. P. Xu, and D. H. Liu, “Protective immunity transferred by infusion of cytomegalovirus-specific CD8+ T cells within donor grafts: its associations with cytomegalovirus reactivation following unmanipulated allogeneic hematopoietic stem cell transplantation,” Biology of Blood and Marrow Transplantation, vol. 16, no. 7, pp. 994–1004, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. B. Faist, B. Fleischer, and M. Jacobsen, “Cytomegalovirus infection- and age-dependent changes in human CD8+ T-cell cytokine expression patterns,” Clinical and Vaccine Immunology, vol. 17, no. 6, pp. 986–992, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Koch, R. Solana, O. D. Rosa, and G. Pawelec, “Human cytomegalovirus infection and T cell immunosenescence: a mini review,” Mechanisms of Ageing and Development, vol. 127, no. 6, pp. 538–543, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. J. E. Kohlmeier, L. M. Connor, A. D. Roberts, T. Cookenham, K. Martin, and D. L. Woodland, “Nonmalignant clonal expansions of memory CD8+ T cells that arise with age vary in their capacity to mount recall responses to infection,” Journal of Immunology, vol. 185, no. 6, pp. 3456–3462, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. F. M. Mattes, A. Vargas, J. Kopycinski et al., “Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation,” American Journal of Transplantation, vol. 8, no. 5, pp. 990–999, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Egli, I. Binet, S. Binggeli et al., “Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients,” Journal of Translational Medicine, vol. 6, article 29, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. L. Krol, J. Stuchly, P. Hubacek, et al., “Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT,” Bone Marrow Transplantation, vol. 46, no. 8, pp. 1089–1098, 2011. View at Publisher · View at Google Scholar
  29. C. Blache, J. M. Chauvin, A. Marie-Cardine et al., “Reduced frequency of regulatory T cells in peripheral blood stem cell compared to bone marrow transplantations,” Biology of Blood and Marrow Transplantation, vol. 16, no. 3, pp. 430–434, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. F. di Rosa and R. Pabst, “The bone marrow: a nest for migratory memory T cells,” Trends in Immunology, vol. 26, no. 7, pp. 360–366, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Tayebi, P. Tiberghien, C. Ferrand et al., “Allogeneic peripheral blood stem cell transplantation results in less alteration of early T cell compartment homeostasis than bone marrow transplantation,” Bone Marrow Transplantation, vol. 27, no. 2, pp. 167–175, 2001. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Storek, M. A. Dawson, B. Storer et al., “Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation,” Blood, vol. 97, no. 11, pp. 3380–3389, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. A. Guerrero, S. R. Riddell, J. Storek, et al., “Cytomegalovirus viral load and virus-specific immune reconstitution after peripheral blood stem cell versus bone marrow transplantation,” Biology of Blood and Marrow Transplantation, vol. 18, no. 1, pp. 66–75, 2012. View at Publisher · View at Google Scholar