Abstract
Impaired recovery of T cell immune function is a major source of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). Although natural immunity (NK cells, monocytes, neutrophils) function normally within weeks after transplant, helper T cell activity and T cell-dependent B cell responses remain impaired for months to years. The etiology of the immune defect is multifactorial. Attempts to reduce graft-versus-host disease (GvHD) through T cell depletion or immunosuppressive drug therapy significantly impair immune reconstitution. GvHD itself has a negative impact on immune function due to both decreased thymopoiesis [1,2] and increased apoptosis of peripheral blood T cells [3,4]. Furthermore, tissue damage from total body irradiation (TBI) and other intensive conditioning regimens damages important stromal elements of the thymus, as well as the BM, secondary lymphoid organs, and other tissues in which T cell generation and proliferation take place. The composite impact of these factors leads to T cell immunodeficiency following allogeneic HSCT, which can contribute to unacceptably high rates of opportunistic infection and relapse. Improving the results of allogeneic HSCT requires better understanding of the mechanisms involved in post-transplant T cell reconstitution.
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References
Hazenberg MD, Otto SA, de Pauw ES, et al. T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events. Blood 2002;99:3449–53.
Weinberg K, Blazar BR, Wagner JE, et al. Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood 2001;97: 1458–66.
Brochu S, Rioux-Masse B, Roy J, Roy DC, Perreault C. Massive activation-induced cell death of alloreactive T cells with apoptosis of bystander post-thymic T cells prevents immune reconstitution in mice with graft-versus-host disease. Blood 1999;94:390–400.
Lin MT, Tseng LH, Frangoul H, et al. Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. Blood 2000;95:3832–39.
Douek DC, Vescio RA, Betts MR, et al. Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet 2000;355:1875–81.
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;100:2235–42.
Chung B, Barbara-Burnham L, Barsky L, Weinberg K. Radiosensitivity of thymic interleukin-7 production and thymopoiesis after bone marrow transplantation. Blood 2001;98:1601–06.
Mclean AR, Michie CA. In vivo estimates of division and death rates of human T lymphocytes. Proc Natl Acad Sci U S A 1995;92:3707–11.
Hamann D, Baars PA, Rep MH, et al. Phenotypic and functional separation of memory and effector human CD8+ T cells. J Exp Med 1997;186:1407–18.
Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998;396:690–95.
Hochberg EP, Chillemi AC, Wu CJ, et al. Quantitation of T-cell neogenesis in vivo after allogeneic bone marrow transplantation in adults. Blood 2001;98:1116–21.
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;95:3990–95.
Bell EB, Sparshott SM, Drayson MT, Ford WL. The stable and permanent expansion of functional T lymphocytes in athymic nude rats after a single injection of mature T cells. J Immunol 1987;139:1379–84.
Martinez C, Urbano-Ispizua A, Rozman C, et al. Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts. Exp Hematol 1999;27:561–68.
Keever CA, Small TN, Flomenberg N, et al. Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts. Blood 1989;73:1340–50.
Mackall CL, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE. Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol 1996;156:4609–16.
Rocha V, von Boehmer H. Peripheral selection of the T cell repertoire. Science 1991;251:1225–28.
Godthelp BC, van Tol MJ, Vossen JM, van den Elsen PJ. T-Cell immune reconstitution in pediatric leukemia patients after allogeneic bone marrow transplantation with T-cell-depleted or unmanipulated grafts: evaluation of overall and antigen-specific T-cell repertoires. Blood 1999;94:4358–69.
Roux E, Helg C, Dumont-Girard F, Chapuis B, Jeannet M, Roosnek E. Analysis of T-cell repopulation after allogeneic bone marrow transplantation: significant differences between recipients of T-cell depleted and unmanipulated grafts. Blood 1996;87:3984–92.
Westermann J, Pabst R. Lymphocyte subsets in the blood: a diagnostic window on the lymphoid system? Immunol Today 1990; 11:406–10.
Morecki S, Gelfand Y, Nagler A, et al. Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen. Bone Marrow Transplant 2001;28:243–49.
Soares MV, Borthwick NJ, Maini MK, Janossy G, Salmon M, Akbar AN. IL-7-dependent extrathymic expansion of CD45RA+ T cells enables preservation of a naive repertoire. J Immunol 1998;161:5909–17.
Tan JT, Dudl E, LeRoy E, et al. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 2001;98:8732–37.
Mackall CL, Fry TJ, Bare C, Morgan P, Galbraith A, Gress RE. IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation. Blood 2001;97:1491–97.
Brocker T. Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class II-expressing dendritic cells. J Exp Med 1997;186:1223–32.
Theilgaard-Monch K, Raaschou-Jensen K, Palm H, et al. Flow cytometric assessment of lymphocyte subsets, lymphoid progenitors, and hematopoietic stem cells in allogeneic stem cell grafts. Bone Marrow Transplant 2001;28: 1073–82.
Storek J, Dawson MA, Storer B, et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood 2001;97:3380–89.
Tayebi H, Tiberghien P, Ferrand C, et al. Allogeneic peripheral blood stem cell transplantation results in less alteration of early T cell compartment homeostasis than bone marrow transplantation. Bone Marrow Transplant 2001; 27:167–75.
Bahceci E, Epperson D, Douek DC, Melenhorst JJ, Childs RC, Barrett AJ. Early reconstitution of the T cell repertoire after peripheral blood stem cell transplantation and nonmyeloablative chemotherapy is from post-thymic T cell expansion and is unaffected by graft-versus-host disease or mixed chimerism. Blood (submitted).
Friedman TM, Varadi G, Hopely DD, et al. Nonmyeloablative conditioning allows for more rapid T-cell repertoire reconstitution following allogeneic matched unrelated bone marrow transplantation compared to myeloablative approaches. Biol Blood Marrow Transplant 2001;7:656–64.
Alpdogan O, Schmaltz C, Muriglan SJ, et al. Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease. Blood 2001;98:2256–65.
Min D, Taylor PA, Panoskaltsis-Mortari A, et al. Protection from thymic epithelial cell injury by keratinocyte growth factor: a new approach to improve thymic and peripheral T-cell reconstitution after bone marrow transplantation. Blood 2002;99:4592–4600.
Solomon SR, Tran T, Carter CS, et al. Optimized clinical scale culture conditions for ex vivo selective depletion of host-reactive donor lymphocytes: a strategy for GvHD prophylaxis in allogeneic peripheral blood stem cell transplantation. Cytotherapy 2002;4:395–406.
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Solomon, S.R., Barrett, A.J. (2003). Reconstituting T Cell Immunity Following Hematopoietic Stem Cell Transplantation. In: Sibinga, C.T.S., De Leij, L.F.M.H. (eds) Cellular Engineering and Cellular Therapies. Developments in Hematology and Immunology, vol 38. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3718-9_14
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DOI: https://doi.org/10.1007/978-1-4757-3718-9_14
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