Altered homeostasis of CD4(+) memory T cells in allogeneic hematopoietic stem cell transplant recipients: Chronic graft-versus-host disease enhances T cell differentiation and exhausts central memory T cell pool
ABSTRACT An increased risk of late infection is a serious complication after allogeneic hematopoietic stem cell transplantation (AHSCT), especially for recipients with defective CD4(+) T cell recovery. Although chronic graft-versus-host disease (cGVHD) negatively influences CD4(+) T cell reconstitution, the mechanisms leading to this defect are not well understood. We found that the proportion of CD27(-) CD4(+) T cells was remarkably increased in ASHCT recipients with cGVHD or with repetitive infectious episodes. Isolated CD27(-) CD4(+) T cells from ASHCT recipients had significantly shortened telomere length, displayed enhanced vulnerability to activation-induced cell death, and showed extremely reduced clonal diversity, when compared with CD27(-) CD4(+) T cells from healthy donors. Also, CD27(+) CD4(+) T cells from AHSCT recipients easily lost their expression of CD27 in response to antigen stimulation regardless of cGVHD status. Taken together, these data indicate that homeostasis of memory CD4(+) T cells from AHSCT recipients is altered, and that they easily transit into CD27(-) effector memory T cells. Increased in vivo T cell stimulation observed in recipients with cGVHD further promotes the transition to effector memory cells, a change that decreases the central memory CD4(+) T cell pool and consequently weakens the recipient's defense against persistently infecting pathogens.
SourceAvailable from: Troy R Torgerson[Show abstract] [Hide abstract]
ABSTRACT: Defective immune reconstitution is a major barrier to successful hematopoietic cell transplantation (HCT), and has important implications in the pediatric population. There are many factors that affect immune recovery, including stem cell source and graft-versus-host disease (GVHD). Complete assessment of immune recovery, including T and B lymphocyte evaluation, innate immunity, and response to neoantigens, may provide insight as to infection risk and optimal time for immunizations. The increasing use of cord blood grafts requires additional study regarding early reconstitution and impact upon survival. Immunization schedules may require modification based upon stem cell source and immune reconstitution, and this is of particular importance as many children have been incompletely immunized, or not at all, before school entry. Additional studies are needed in children post-HCT to evaluate the impact of differing stem cell sources upon immune reconstitution, infectious risks, and immunization responses.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2011; 18(1):6-15. DOI:10.1016/j.bbmt.2011.11.014 · 3.35 Impact Factor
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ABSTRACT: Telomeres are long (TTAGGG)(n) nucleotide repeats and an associated protein complex located at the end of the chromosomes. They shorten with every cell division and, thus are markers for cellular aging, senescence, and replicative capacity. Telomere dysfunction is linked to several bone marrow disorders, including dyskeratosis congenita, aplastic anemia, myelodysplastic syndrome, and hematopoietic malignancies. Hematopoietic stem cell transplantation (HSCT) provides an opportunity in which to study telomere dynamics in a high cell proliferative environment. Rapid telomere shortening of donor cells occurs in the recipient shortly after HSCT; the degree of telomere attrition does not appear to differ by graft source. As expected, telomeres are longer in recipients of grafts with longer telomeres (e.g., cord blood). Telomere attrition may play a role in, or be a marker of, long term outcome after HSCT, but these data are limited. In this review, we discuss telomere biology in normal and abnormal hematopoiesis, including HSCT.Blood reviews 07/2011; 25(6):261-9. DOI:10.1016/j.blre.2011.06.004 · 5.45 Impact Factor
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ABSTRACT: Mononuclear phenylglyoxylato- and 4-R-benzoatocopper(II) complexes with two different 1,3-bis(2-arylimino)isoindoline ligands (aryl = pyridyl, or benzimidazolyl) have been synthesized and characterized. Coordination mode of the carboxylate ligands is very similar (monodentate) in each case, while redox behavior of the copper center is dependent on the aryl- and 4-R-substituents. The supramolecular assembly in the solid state via hydrogen bonds and π-stacking between the ligands can be influenced by the aryl-group and carboxylate ligand.Inorganic Chemistry Communications 11/2011; 14(11):1767-1772. DOI:10.1016/j.inoche.2011.08.005 · 2.06 Impact Factor