title: Lymphopoiesis, apoptosis, and immune amnesia.
abstract: Bone marrow transplant recipients have a functional T-cell deficit long after T-cell counts have returned to normal levels. Early after BMT, T-cell phenotype is predominantly CD45RO+/CD29high/HLA-DR+/CD38high. This profile is associated with activated memory cells in healthy subjects, but also appears on the earliest mature naive T-cells in times of lymphopoietic stress. Most of these cells apoptose in short-term unstimulated culture, suggesting that they would have had a similar fate in vivo. Twelve to 24 months after BMT, CD45RA+/CD29low/HLA-DR-/CD38low T cells increase, apoptosis decreases, and T-cell function normalizes. We hypothesize that in the adult, mature memory T cells regulate their own replacement by rescuing a proportion of newly generated naive cells from apoptosis. Ablation of memory cells consequent to high dose therapy disrupts this process, resulting in a protracted period of high lymphocyte turnover with few cells surviving to make the antigen-driven transition to memory cells. Infection with HIV-1 also eventuates in immune deficiency associated with a loss in CD4+ T cells and dominance of the phenotypic/apoptotic profile which we have associated with lymphopoietic stress. Recent data independently confirm that T-cell turnover is greatly elevated in HIV infection. Catastrophic or chronic depletion of memory T cells due to marrow ablative therapy or HIV-1 infection interferes with memory replacement, substituting short-lived hypofunctional naive T cells which characterize the state of immune amnesia.
authors.affiliation: University of Pittsburgh School of Medicine, Department of Medicine, Pennsylvania 15213, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Donnenberg
authors.forename: J B
authors.initials: JB
authors.lastname: Margolick
authors.forename: V S
authors.initials: VS
authors.lastname: Donnenberg
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000328:Adult; D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D015497:HIV-1; D006410:Hematopoiesis; D006801:Humans; D007156:Immunologic Memory; D013601:T-Lymphocytes