title: Telomerase activation and rejuvenation of telomere length in stimulated T cells derived from serially transplanted hematopoietic stem cells.
abstract: Telomeres shorten in hematopoietic cells, including hematopoietic stem cells (HSCs), during aging and after transplantation, despite the presence of readily detectable levels of telomerase in these cells. In T cells, antigenic stimulation has been shown to result in a marked increase in the level of telomerase activity. We now show that stimulation of T cells derived from serially transplanted HSC results in a telomerase-dependent elongation of telomere length to a size similar to that observed in T cells isolated directly from young mice. Southern analysis of telomere length in resting and anti-CD3/CD28 stimulated donor-derived splenic T cells revealed an increase in telomere size by approximately 7 kb for the population as a whole. Stimulation of donor-derived T cells from recipients of HSCs from telomerase-deficient mice did not result in regeneration of telomere length, demonstrating a dependence on telomerase. Furthermore, clonal anti-CD3/CD28 stimulation of donor-derived T cells followed by fluorescent in situ hybridization (FISH) analysis of telomeric signal intensity showed that telomeres had increased in size by approximately 50% for all clonal expansions. Together, these results imply that one role for telomerase in T cells may be to renew or extend replicative potential via the rejuvenation of telomere length.
authors.affiliation: Beckman Center, Pathology Department, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA. rallsopp@stanford.edu
authors.forename: Richard C
authors.initials: RC
authors.lastname: Allsopp
authors.forename: Samuel
authors.initials: S
authors.lastname: Cheshier
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D018380:Hematopoietic Stem Cell Transplantation; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000502:physiology*; D019098:Telomerase / Q000502:physiology*; D016615:Telomere; D035321:Telomeric Repeat Binding Protein 1 / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase