CMV reactivation drives posttransplant T-cell reconstitution and results in defects in the underlying TCRβ repertoire

Blood

Volumn 125, Issue 25, 2015, Pages 3835-3850

  Suessmuth, Yvonne ^a   Mukherjee, Rithun ^b,c   Watkins, Benjamin ^d   Koura, Divya T ^e   Finstermeier, Knut ^f   Desmarais, Cindy ^f   Stempora, Linda ^a   Horan, John T ^d   Langston, Amelia ^e   Qayed, Muna ^d   Khoury, Hanna J ^e   Grizzle, Audrey ^d   Cheeseman, Jennifer A ^a   Conger, Jason A ^a   Robertson, Jennifer ^a   Garrett, Aneesah ^d   Kirk, Allan D ^a   Waller, Edmund K ^e   Blazar, Bruce R ^g   Mehta, Aneesh K ^a   Robins, Harlan S ^b   Kean, Leslie S ^b,c,d,h   more..

^a EMORY UNIVERSITY   (United States)

^b Fred Hutchinson Cancer Research Center   (United States)

^c SEATTLE CHILDREN S RESEARCH INSTITUTE   (United States)

^d EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e EMORY UNIVERSITY   (United States)

^f Adaptive Biotechnologies Corp   (United States)

^g UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^h UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABATACEPT; CD28 ANTIGEN; CD31 ANTIGEN; CD4 ANTIGEN; CD57 ANTIGEN; CYCLOSPORIN; GANCICLOVIR; GRANZYME B; METHOTREXATE; T LYMPHOCYTE RECEPTOR BETA CHAIN; VALGANCICLOVIR; LYMPHOCYTE ANTIGEN RECEPTOR;

ADOLESCENT; ADULT; AGED; ANTIVIRAL THERAPY; ARTICLE; CD8+ T LYMPHOCYTE; CELL EXPANSION; CELL SELECTION; CHILD; CLINICAL ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTION; FEMALE; FLOW CYTOMETRY; GRAFT VERSUS HOST REACTION; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HIGH THROUGHPUT SEQUENCING; HUMAN; IMMUNE DYSREGULATION; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTE CLONE; LYMPHOCYTE FUNCTION; MALE; MEMORY T LYMPHOCYTE; PRIORITY JOURNAL; PROSPECTIVE STUDY; SCHOOL CHILD; T LYMPHOCYTE SUBPOPULATION; VIRUS REACTIVATION; YOUNG ADULT; ALLOTRANSPLANTATION; CLINICAL TRIAL; IMMUNOLOGY; MIDDLE AGED; PHYSIOLOGY; VIRUS ACTIVATION;

ADOLESCENT; ADULT; AGED; CD8-POSITIVE T-LYMPHOCYTES; CHILD; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; FEMALE; FLOW CYTOMETRY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MALE; MIDDLE AGED; RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA; TRANSPLANTATION, HOMOLOGOUS; VIRUS ACTIVATION; YOUNG ADULT;

EID: 84930593753     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2015-03-631853     Document Type: Article

References (65)

1. Guerrero A, Riddell SR, Storek J, et al. Cytomegalovirus viral load and virus-specific immune reconstitution after peripheral blood stem cell versus bone marrow transplantation. Biol Blood Marrow Transplant. 2012;18(1):66-75.
2. Jordan CT, Roback JD. Separating antiviral and GVHD activities of donor T cells prior to bone marrow transplantation. Immunol Res. 2004;29(1-3):209-218.
3. Servais S, Lengline E, Porcher R, et al. Long term immune reconstitution and infection burden after mismatched hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(4):507-517.
4. Small TN, Cowan MJ. Immunization of hematopoietic stem cell transplant recipients against vaccine-preventable diseases. Expert Rev Clin Immunol. 2011;7(2):193-203.
5. Abu-Khader A, Krause S. Rapid monitoring of immune reconstitution after allogeneic stem cell transplantation - a comparison of different assays for the detection of cytomegalovirus-specific T cells. Eur J Haematol. 2013;91(6):534-545.
6. Brown JA, Stevenson K, Kim HT, et al. Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis. Blood. 2010;115(20):4111-4119.
7. Bunse CE, Borchers S, Varanasi PR, et al. Impaired functionality of antiviral T cells in G-CSF mobilized stem cell donors: implications for the selection of CTL donor. PLoS ONE. 2013;8(12):e77925.
8. McGoldrick SM, Bleakley ME, Guerrero A, et al. Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo. Blood. 2013;121(14):2796-2803.
9. Torelli GF, Lucarelli B, Iori AP, et al. The immune reconstitution after an allogeneic stem cell transplant correlates with the risk of graft-versus-host disease and cytomegalovirus infection. Leuk Res. 2011;35(8):1124-1126.
10. Boeckh M, Nichols WG. The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood. 2004;103(6):2003-2008.
11. Boeckh M, Nichols WG, Papanicolaou G, Rubin R, Wingard JR, Zaia J. Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003;9(9):543-558.
12. Green ML, Leisenring W, Stachel D, et al. Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(11):1687-1699.
13. Marty FM, Bryar J, Browne SK, et al. Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis. Blood. 2007;110(2):490-500.
14. Marty FM, Ljungman P, Papanicolaou GA, et al Maribavir 1263-300 Clinical Study Group. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis. 2011;11(4):284-292.
15. Marty FM, Winston DJ, Rowley SD, et al; CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227-1236.
16. Boeckh M. Complications, diagnosis, management, and prevention of CMV infections: current and future. Hematology Am Soc Hematol Educ Program. 2011;2011:305-309.
17. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Infect Dis Clin North Am. 2010;24(2):319-337.
18. Green ML, Leisenring WM, Xie H, et al. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia. Blood. 2013;122(7):1316-1324.
19. Gratama JW, Boeckh M, Nakamura R, et al. Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study. Blood. 2010;116(10):1655-1662.
20. Ozdemir E, St John LS, Gillespie G, et al. Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells. Blood. 2002;100(10):3690-3697.
21. Gratama JW, Brooimans RA, van der Holt B, et al. Monitoring cytomegalovirus IE-1 and pp65-specific CD4+ and CD8+ T-cell responses after allogeneic stem cell transplantation may identify patients at risk for recurrent CMV reactivations. Cytometry B Clin Cytom. 2008;74(4):211-220.
22. Gratama JW, van Esser JW, Lamers CH, et al. Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection. Blood. 2001;98(5):1358-1364.
23. Koura DT, Horan JT, Langston AA, et al. In vivo T cell costimulation blockade with abatacept for acute graft-versus-host disease prevention: a first-in-disease trial. Biol Blood Marrow Transplant. 2013;19(11):1638-1649.
24. Carlson CS, Emerson RO, Sherwood AM, et al. Using synthetic templates to design an unbiased multiplex PCR assay. Nat Commun. 2013;4:2680.
25. Robins HS, Campregher PV, Srivastava SK, et al. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood. 2009;114(19):4099-4107.
26. Robins HS, Srivastava SK, Campregher PV, et al. Overlap and effective size of the human CD8+ T cell receptor repertoire. Sci Transl Med. 2010;2(47):47ra64.
27. Lê Cao KA, Boitard S, Besse P. Sparse PLS discriminant analysis: biologically relevant feature selection and graphical displays for multiclass problems. BMC Bioinformatics. 2011;12:253.
28. Khan N, Shariff N, Cobbold M, et al. Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol. 2002;169(4):1984-1992.
29. Hadrup SR, Strindhall J, Køllgaard T, et al. Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol. 2006;176(4):2645-2653.
30. Verfuerth S, Peggs K, Vyas P, Barnett L, O'Reilly RJ, Mackinnon S. Longitudinal monitoring of immune reconstitution by CDR3 size spectratyping after T-cell-depleted allogeneic bone marrow transplant and the effect of donor lymphocyte infusions on T-cell repertoire. Blood. 2000;95(12):3990-3995.
31. Wu CJ, Chillemi A, Alyea EP, et al. Reconstitution of T-cell receptor repertoire diversity following T-cell depleted allogeneic bone marrow transplantation is related to hematopoietic chimerism. Blood. 2000;95(1):352-359.
32. van Heijst JW, Ceberio I, Lipuma LB, et al. Quantitative assessment of T cell repertoire recovery after hematopoietic stem cell transplantation. Nat Med. 2013;19(3):372-377.
33. Ekström M. Quantifying spatial patterns of landscapes. Ambio. 2003;32(8):573-576.
34. Gastwirth JL. The estimation of the Lorenz curve and Gini index. Rev Econ Stat. 1972;306-316.
35. Komanduri KV, Donahoe SM, Moretto WJ, et al. Direct measurement of CD4+ and CD8+ T-cell responses to CMV in HIV-1-infected subjects. Virology. 2001;279(2):459-470.
36. Lacey SF, Villacres MC, La Rosa C, et al. Relative dominance of HLA-B∗07 restricted CD8+ T-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A∗02 and HLA-B∗07 alleles. Hum Immunol. 2003;64(4):440-452.
37. Bihl F, Frahm N, Di Giammarino L, et al. Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses. J Immunol. 2006;176(7):4094-4101.
38. Knight A, Madrigal AJ, Grace S, et al. The role of Vδ2-negative γδ T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation. Blood. 2010;116(12):2164-2172.
39. Weekes MP, Wills MR, Sissons JG, Carmichael AJ. Long-term stable expanded human CD4+ T cell clones specific for human cytomegalovirus are distributed in both CD45RAhigh and CD45ROhigh populations. J Immunol. 2004;173(9):5843-5851.
40. Junge S, Kloeckener-Gruissem B, Zufferey R, et al. Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. Eur J Immunol. 2007;37(11):3270-3280.
41. Kimmig S, Przybylski GK, Schmidt CA, et al. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J Exp Med. 2002;195(6):789-794.
42. Komanduri KV, St John LS, de Lima M, et al. Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing. Blood. 2007;110(13):4543-4551.
43. Numazaki K, DeStephano L, Wong I, Goldman H, Spira B, Wainberg MA. Replication of cytomegalovirus in human thymic epithelial cells. Med Microbiol Immunol (Berl). 1989;178(2):89-98.
44. Davis CC, Marti LC, Sempowski GD, Jeyaraj DA, Szabolcs P. Interleukin-7 permits Th1/Tc1 maturation and promotes ex vivo expansion of cord blood T cells: a critical step toward adoptive immunotherapy after cord blood transplantation. Cancer Res. 2010;70(13):5249-5258.
45. Thiant S, Labalette M, Trauet J, et al. Plasma levels of IL-7 and IL-15 after reduced intensity conditioned allo-SCT and relationship to acute GVHD. Bone Marrow Transplant. 2011;46(10):1374-1381.
46. van der Velden AM, Claessen AM, van Velzen-Blad H, et al. Vaccination responses and lymphocyte subsets after autologous stem cell transplantation. Vaccine. 2007;25(51):8512-8517.
47. Komatsuda M. Changes of lymphocyte subsets in leukemia patients who received allogenic bone marrow transplantation. Acta Med Okayama. 1991;45(4):257-265.
48. Roberts MM, To LB, Gillis D, et al. Immune reconstitution following peripheral blood stem cell transplantation, autologous bone marrow transplantation and allogeneic bone marrow transplantation. Bone Marrow Transplant. 1993;12(5):469-475.
49. Hebib NC, Déas O, Rouleau M, et al. Peripheral blood T cells generated after allogeneic bone marrow transplantation: lower levels of bcl-2 protein and enhanced sensitivity to spontaneous and CD95-mediated apoptosis in vitro. Abrogation of the apoptotic phenotype coincides with the recovery of normal naive/primed T-cell profiles. Blood. 1999;94(5):1803-1813.
50. Maury S, Mary JY, Rabian C, et al. Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients. Br J Haematol. 2001;115(3):630-641.
51. Pavletic ZS, Joshi SS, Pirruccello SJ, et al. Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies. Bone Marrow Transplant. 1998;21(1):33-41.
52. Gorochov G, Debré P, Leblond V, Sadat-Sowti B, Sigaux F, Autran B. Oligoclonal expansion of CD8+ CD57+ T cells with restricted T-cell receptor beta chain variability after bone marrow transplantation. Blood. 1994;83(2):587-595.
53. Horiuchi T, Hirokawa M, Kawabata Y, et al. Identification of the T cell clones expanding within both CD8(+)CD28(+) and CD8(+)CD28(-) T cell subsets in recipients of allogeneic hematopoietic cell grafts and its implication in post-transplant skewing of T cell receptor repertoire. Bone Marrow Transplant. 2001;27(7):731-739.
54. Mollet L, Fautrel B, Leblond V, et al. Leukemic CD3+ LGL share functional properties with their CD8+ CD57+ cell counterpart expanded after BMT. Leukemia. 1999;13(2):230-240.
55. Sauce D, Larsen M, Fastenackels S, et al. Evidence of premature immune aging in patients thymectomized during early childhood. J Clin Invest. 2009;119(10):3070-3078.
56. Sylwester AW, Mitchell BL, Edgar JB, et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202(5):673-685.
57. Mekker A, Tchang VS, Haeberli L, Oxenius A, Trkola A, Karrer U. Immune senescence: relative contributions of age and cytomegalovirus infection. PLoS Pathog. 2012;8(8):e1002850.
58. Vezys V, Yates A, Casey KA, et al. Memory CD8 T-cell compartment grows in size with immunological experience. Nature. 2009;457(7226):196-199.
59. Lewin SR, Heller G, Zhang L, et al. Direct evidence for new T-cell generation by patients after either T-cell-depleted or unmodified allogeneic hematopoietic stem cell transplantations. Blood. 2002;100(6):2235-2242.
60. Weinberg K, Blazar BR, Wagner JE, et al. Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood. 2001;97(5):1458-1466.
61. Agus DB, Surh CD, Sprent J. Reentry of T cells to the adult thymus is restricted to activated T cells. J Exp Med. 1991;173(5):1039-1046.
62. Krenger W, Holländer GA. The immunopathology of thymic GVHD. Semin Immunopathol. 2008;30(4):439-456.
63. Mocarski ES, Bonyhadi M, Salimi S, McCune JM, Kaneshima H. Human cytomegalovirus in a SCIDhu mouse: thymic epithelial cells are prominent targets of viral replication. Proc Natl Acad Sci USA. 1993;90(1):104-108.
64. Storek J, Joseph A, Dawson MA, Douek DC, Storer B, Maloney DG. Factors influencing T-lymphopoiesis after allogeneic hematopoietic cell transplantation. Transplantation. 2002;73(7):1154-1158.
65. Storek J, Joseph A, Espino G, et al. Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation. Blood. 2001;98(13):3505-3512.