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.