Search

It is well-known that the functioning of the immune system gradually deteriorates with age, and we are increasingly confronted with its consequences as the life expectancy of the human population increases. Changes in the T-cell pool are among the most prominent features of the changing immune system during healthy ageing, and changes in the naive T-cell pool in particular are generally held responsible for its gradual deterioration. These changes in the naive T-cell pool are thought to be due to involution of the thymus. It is commonly believed that the gradual loss of thymic output induces compensatory mechanisms to maintain the number of naive T cells at a relatively constant level, and induces a loss of diversity in the T-cell repertoire. Here we review the studies that support or challenge this widely-held view of immune ageing and discuss the implications for vaccination strategies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Latent infection with cytomegalovirus (CMV) is assumed to contribute to the age-associated decline of the immune system. CMV induces large changes in the T-cell pool and may thereby affect other immune responses. CMV is expected to impact especially older adults, who are already at higher risk of severe disease and hospitalization upon infections such as influenza virus (IAV) infection. Here, we investigated the impact of CMV infection on IAV-specific CD8 + T-cell frequencies in healthy individuals (n=96) and the response to IAV infection in older adults (n=72). IAV-specific memory T-cell frequencies were lower in healthy CMV + older individuals compared to healthy CMV - older individuals. Upon acute IAV infection, CMV serostatus or CMV-specific antibody levels were not negatively associated with IAV-specific T-cell frequencies, function, phenotype or T-cell receptor repertoire diversity. This suggests that specific T-cell responses upon acute IAV infection are not negatively affected by CMV. In addition, we found neither an association between CMV infection and inflammatory cytokine levels in serum during acute IAV infection nor between cytokine levels and the height of the IAV-specific T-cell response upon infection. Finally, CMV infection was not associated with increased severity of influenza-related symptoms. In fact, CMV infection was even associated with increased IAV-specific T-cell responses early upon acute IAV infection. In conclusion, although associated with lower frequencies of memory IAV-specific T cells in healthy individuals, CMV infection does not seem to hamper the induction of a proper T-cell response during acute IAV infection in older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van den Berg, Lanfermeijer, Jacobi, Hendriks, Vos, van Schuijlenburg, Nanlohy, Borghans, van Beek, van Baarle and de Wit.)

Memory T-cells are essential to maintain long-term immunological memory. It is widely thought that the bone marrow (BM) plays an important role in the long-term maintenance of memory T-cells. There is controversy however on the longevity and recirculating kinetics of BM memory T-cells. While some have proposed that the BM is a reservoir for long-lived, non-circulating memory T-cells, it has also been suggested to be the preferential site for memory T-cell self-renewal. In this study, we used in vivo deuterium labeling in goats to simultaneously quantify the average turnover rates-and thereby expected lifespans-of memory T-cells from BM, blood and lymph nodes (LN). While the fraction of Ki-67 positive cells, a snapshot marker for recent cell division, was higher in memory T-cells from blood compared to BM and LN, in vivo deuterium labeling revealed no substantial differences in the expected lifespans of memory T-cells between these compartments. Our results support the view that the majority of memory T-cells in the BM are self-renewing as fast as those in the periphery, and are continuously recirculating between the blood, BM, and LN.

An association between T-cell lymphopenia and autoimmunity has long been proposed, but it remains to be elucidated whether T-cell lymphopenia affects B-cell responses to autoantigens. Human neonatal thymectomy (Tx) results in a decrease in T-cell numbers and we used this model to study the development of autoreactivity. Two cohorts of neonatally thymectomized individuals were examined, a cohort of young (1-5 years post-Tx, n = 10-27) and older children (>10 years, n = 26), and compared to healthy age-matched controls. T-cell and B-cell subsets were assessed and autoantibody profiling performed. Early post-Tx, a decrease in T-cell numbers (2.75 × 10 9 /L vs. 0.71 × 10 9 /L) and an increased proportion of memory T cells (19.72 vs. 57.43%) were observed. The presence of autoantibodies was correlated with an increased proportion of memory T cells in thymectomized children. No differences were seen in percentages of different B-cell subsets between the groups. The autoantigen microarray showed a skewed autoantibody response after Tx. In the cohort of older individuals, autoantibodies were present in 62% of the thymectomized children, while they were found in only 33% of the healthy controls. Overall, our data suggest that neonatal Tx skews the autoantibody profile. Preferential expansion and preservation of Treg (regulatory T) cell stability and function, may contribute to preventing autoimmune disease development after Tx., (© 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)