Assessing ageing of individual T lymphocytes: mission impossible?
Effector T lymphocytes are the progeny of a limited number of antigen-specific precursor cells and it has been estimated that clonotypic human T cells may expand million fold on their way reaching high cell numbers that are sufficient for immune protection. Moreover, memory T cell responses are characterized by repetitive expansion of antigen-specific T cell clonotypes, and limitations in the proliferative capacity could lead to immune senescence. Because telomeres progressively shorten as a function of cell division, telomere length is a powerful indicator of the replicative in vivo history of human T lymphocytes. In this review, we summarize observations made over the last decade on telomere length dynamics of well-defined T cell populations derived from healthy donors and patients with infectious disease or cancer. We focus on T cell differentiation, T cell ageing, and natural and vaccine induced immune responses. We also discuss the scientific evidence for in vivo replicative senescence of antigen-specific T cells, and evaluate the available methods for measuring telomere lengths and telomerase activity, and their potential and limitations to increase our understanding of T cell physiology.
Division of Experimental Oncology, Multidisciplinary Oncology Center CePO, Avenue Pierre-Decker 4, CH-1005 Lausanne, Switzerland.
Emanuela M
EM
Iancu
Daniel E
DE
Speiser
Nathalie
N
Rufer
D019264:Adoptive Transfer; D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D016922:Cellular Senescence; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D014612:Vaccines / Q000276:immunology
D014612:Vaccines