New Insights into Lymphocyte Differentiation and Aging from Telomere Length and Telomerase Activity Measurements

Abstract

ab CD8 + , gd, and NK lymphocytes are fundamental effector cells against viruses and tumors. These cells can be divided into multiple subsets according to their phenotype. Based on progressive telomere attrition from naive to late effector memory cells, human CD8 + T cell subsets have been positioned along a pathway of differentiation, which is also considered as a process of lymphocyte aging or senescence. A similar categorization has not been clearly established for gd and NK cell populations. Moreover, the distinction between the aging of these populations due to cellular differentiation or due to the chronological age of the donor has not been formally considered. In this study, we performed systematic measurements of telomere length and telomerase activity in human ab CD8 + , gd, and NK lymphocytes based on subset division and across age to address these points and better understand the dichotomy between differentiation and temporal aging. This approach enables us to position phenotypically distinct gd or NK subsets along a putative pathway of differentiation, such as for CD8 + T cells. Moreover, our data show that both cellular differentiation and donor aging have profound but independent effects on telomere length and telomerase activity of lymphocyte subpopulations, implying distinct mechanisms and consequences on the immune system.

Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients

“…CD57 expression in NK cells has been related to terminal differentiation and reduced proliferative potential, illustrated by their shorter telomere length . Increased circulating CD57+ NK cells are associated with immune senescence, a process that may develop independently of chronological age as shown for patients with end‐stage renal disease (ESRD) .…”

“…CD57 expression in NK cells has been related to terminal differentiation and reduced proliferative potential, illustrated by their shorter telomere length. [46][47][48] Increased circulating CD57+…”

Innate Immune Responses in the Outcome of Haploidentical Hematopoietic Stem Cell Transplantation to Cure Hematologic Malignancies

“…On the other hand, CD56 dim /CD16 pos (CD56 dim ) NK cells are the largest NK cell subset in PB (up to 95%) and mainly exert cytototoxic functions via the secretion of lytic granules (104, 126–128). CD56 br and CD56 dim are also considered two sequential stages of NK cell maturation with the latter subset being the terminally-differentiation one characterized by shortest telomere length (120, 121, 129, 130). CD56 br NK cells usually show high levels of CD94/NKG2A, while almost lack KIRs (131).…”

Bi-allelic MCM10 mutations cause telomere shortening with immune dysfunction and cardiomyopathy

“…Interestingly, Mcm10 was identified as an RTEL1interacting protein in mass spectrometry analyses of murine cells (Vannier et al, 2013), arguing that a shared requirement for telomere replication may underlie NKD observed in these patients. Finally, limited evidence suggests that NK cells have shorter telomeres than T-and B-cells, although they arise from a common progenitor, and that telomerase activity decreases as NK cells differentiate (Fali et al, 2019, Ouyang et al, 2007, Romagnani et al, 2007. These phenotypes may explain why the NK cell lineage is particularly sensitive to defects in telomere replication.…”