Reconstituting T Cell Immunity Following Hematopoietic Stem Cell Transplantation
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.
KeywordsHematopoietic Stem Cell Transplantation Immune Reconstitution Peripheral Blood Stem Cell Transplantation Preparative Regimen Allogeneic Haematopoietic Stem Cell Transplantation
- 12.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.PubMedGoogle Scholar
- 18.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.PubMedGoogle Scholar
- 29.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).Google Scholar
- 30.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.PubMedCrossRefGoogle Scholar