Quantifiable blood TCR repertoire components associate with immune aging

Ventura, M. T., Casciaro, M., Gangemi, S. & Buquicchio, R. Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clin. Mol. Allergy 15, 21 (2017).Article 

Google Scholar 
Shaw, A. C., Joshi, S., Greenwood, H., Panda, A. & Lord, J. M. Aging of the innate immune system. Curr. Opin. Immunol. 22, 507–513 (2010).Article 
CAS 

Google Scholar 
Weiskopf, D., Weinberger, B. & Grubeck-Loebenstein, B. The aging of the immune system. Transpl. Int 22, 1041–1050 (2009).Article 
CAS 

Google Scholar 
Chen, K. & Kolls, J. K. T cell-mediated host immune defenses in the lung. Annu Rev. Immunol. 31, 605–633 (2013).Article 
CAS 

Google Scholar 
Farhood, B., Najafi, M. & Mortezaee, K. CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: A review. J. Cell Physiol. 234, 8509–8521 (2019).Article 
CAS 

Google Scholar 
Mogilenko, D. A. et al. Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK(+) CD8(+) T Cells as Conserved Hallmark of Inflammaging. Immunity 54, 99–115 e12 (2021).Article 
CAS 

Google Scholar 
Yano, T. et al. Surgical Outcomes of Postural Instability in Patients With Cervical Myelopathy. Clin. Spine Surg. 33, E466–E471 (2020).Article 

Google Scholar 
Liang, Z., Dong, X., Zhang, Z., Zhang, Q. & Zhao, Y. Age-related thymic involution: Mechanisms and functional impact. Aging Cell 21, e13671 (2022).Article 
CAS 

Google Scholar 
Britanova, O. V. et al. Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling. J. Immunol. 192, 2689–2698 (2014).Article 
CAS 

Google Scholar 
Colonna-Romano, G. et al. Impairment of gamma/delta T lymphocytes in elderly: implications for immunosenescence. Exp. Gerontol. 39, 1439–1446 (2004).Article 
CAS 

Google Scholar 
van der Geest, K. S. M. et al. Impact of Aging on the Frequency, Phenotype, and Function of CD161-Expressing T Cells. Front Immunol. 9, 752 (2018).Article 

Google Scholar 
Britanova, O. V. et al. Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians. J. Immunol. 196, 5005–5013 (2016).Article 
CAS 

Google Scholar 
Qi, Q. et al. Diversity and clonal selection in the human T-cell repertoire. Proc. Natl. Acad. Sci. USA 111, 13139–13144 (2014).Article 
ADS 
CAS 

Google Scholar 
Zhuo, Y. et al. Evaluation and comparison of adaptive immunity through analyzing the diversities and clonalities of T-cell receptor repertoires in the peripheral blood. Front Immunol. 13, 916430 (2022).Article 
CAS 

Google Scholar 
Mittelbrunn, M. & Kroemer, G. Hallmarks of T cell aging. Nat. Immunol. 22, 687–698 (2021).Article 
CAS 

Google Scholar 
de Greef, P. C. et al. The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes. Elife 9, e49900 (2020).Weng, N. P. Numbers and odds: TCR repertoire size and its age changes impacting on T cell functions. Semin Immunol. 69, 101810 (2023).Article 
CAS 

Google Scholar 
Yoshida, K. et al. Aging-related changes in human T-cell repertoire over 20years delineated by deep sequencing of peripheral T-cell receptors. Exp. Gerontol. 96, 29–37 (2017).Article 
CAS 

Google Scholar 
Sun, X. et al. Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets. J. Clin. Invest 132, e158122 (2022).Laydon, D. J., Bangham, C. R. & Asquith, B. Estimating T-cell repertoire diversity: limitations of classical estimators and a new approach. Philos Trans. R Soc. Lond B Biol. Sci. 370, (2015).Yu, X. et al. Quantifiable TCR repertoire changes in prediagnostic blood specimens among patients with high-grade ovarian cancer. Cell Rep. Med. 5, 101612 (2024).Article 
CAS 

Google Scholar 
Nolan, S. et al. A large-scale database of T-cell receptor beta (TCRbeta) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2. Res Sq, Preprint (2020).Emerson, R. O. et al. Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat. Genet 49, 659–665 (2017).Article 
CAS 

Google Scholar 
Mitchell, A. M. et al. Temporal development of T cell receptor repertoires during childhood in health and disease. JCI Insight 7 (2022).Madi, A. et al. T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences. Elife 6, (2017).Fischer, S., Stanke, F. & Tummler, B. VJ Segment Usage of TCR-Beta Repertoire in Monozygotic Cystic Fibrosis Twins. Front Immunol. 12, 599133 (2021).Article 
CAS 

Google Scholar 
Cader, F. Z. et al. A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma. Nat. Med. 26, 1468–1479 (2020).Article 
CAS 

Google Scholar 
Emerson, R. et al. Estimating the ratio of CD4+ to CD8+ T cells using high-throughput sequence data. J. Immunol. Methods 391, 14–21 (2013).Article 
CAS 

Google Scholar 
DeWitt, W. S. et al. Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity. Elife 7 (2018).Le Bourhis, L. et al. Mucosal-associated invariant T cells: unconventional development and function. Trends Immunol. 32, 212–218 (2011).Article 

Google Scholar 
Matsuoka, T. et al. The effects of 5-OP-RU stereochemistry on its stability and MAIT-MR1 axis. Chembiochem 22, 672–678 (2021).Article 
CAS 

Google Scholar 
Xiao, X. & Cai, J. Mucosal-Associated Invariant T Cells: New Insights into Antigen Recognition and Activation. Front Immunol. 8, 1540 (2017).Article 

Google Scholar 
Dong, S. et al. The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes. JCI Insight 6, e147474 (2021).Garner, L. C. et al. Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity. Nat. Immunol. 24, 1565–1578 (2023).Article 
CAS 

Google Scholar 
Pais Ferreira, D. et al. Central memory CD8(+) T cells derive from stem-like Tcf7(hi) effector cells in the absence of cytotoxic differentiation. Immunity 53, 985–1000 e11 (2020).Article 
CAS 

Google Scholar 
Yao, C. et al. BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8(+) T cells. Nat. Immunol. 22, 370–380 (2021).Article 
CAS 

Google Scholar 
Vodnala, S. K. et al. T cell stemness and dysfunction in tumors are triggered by a common mechanism. Science 363 (2019).Gattinoni, L. et al. A human memory T cell subset with stem cell-like properties. Nat. Med. 17, 1290–1297 (2011).Article 
CAS 

Google Scholar 
Qiu, X. et al. Single-cell mRNA quantification and differential analysis with Census. Nat. Methods 14, 309–315 (2017).Article 
CAS 

Google Scholar 
Gulati, G. S. et al. Single-cell transcriptional diversity is a hallmark of developmental potential. Science 367, 405–411 (2020).Article 
ADS 
CAS 

Google Scholar 
Van de Sande, B. et al. A scalable SCENIC workflow for single-cell gene regulatory network analysis. Nat. Protoc. 15, 2247–2276 (2020).Article 

Google Scholar 
Greenberger, L. M. et al. Anti-spike T-cell and Antibody Responses to SARS-CoV-2 mRNA Vaccines in Patients with Hematologic Malignancies. Blood Cancer Discov. 3, 481–489 (2022).Article 
CAS 

Google Scholar 
Gittelman, R. M. et al. Longitudinal analysis of T cell receptor repertoires reveals shared patterns of antigen-specific response to SARS-CoV-2 infection. JCI Insight 7, e151849 (2022).DeWolf, S. et al. Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse. Sci. Transl. Med. 15, eabq0476 (2023).Article 
CAS 

Google Scholar 
Towlerton, A. M. H., Ravishankar, S., Coffey, D. G., Puronen, C. E. & Warren, E. H. Serial Analysis of the T-Cell Receptor beta-Chain Repertoire in People Living With HIV Reveals Incomplete Recovery After Long-Term Antiretroviral Therapy. Front Immunol. 13, 879190 (2022).Article 
CAS 

Google Scholar 
Kearns, N., Maijers, I., Harper, J., Beasley, R. & Weatherall, M. Inhaled Corticosteroids in Acute Asthma: A Systemic Review and Meta-Analysis. J. Allergy Clin. Immunol. Pr. 8, 605–617 e6 (2020).Article 

Google Scholar 
Jiang, Y., Li, Y. & Zhu, B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis. 6, e1792 (2015).Article 
CAS 

Google Scholar 
Chabner, B. A. & Roberts, T. G. Jr Timeline: Chemotherapy and the war on cancer. Nat. Rev. Cancer 5, 65–72 (2005).Article 
CAS 

Google Scholar 
Sacco, K. et al. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nat. Med. 28, 1050–1062 (2022).Article 
CAS 

Google Scholar 
Kanakry, C. G. et al. Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide. JCI Insight 1, e86252 (2016).Pagliuca, S. et al. The similarity of class II HLA genotypes defines patterns of autoreactivity in idiopathic bone marrow failure disorders. Blood 138, 2781–2798 (2021).Article 
CAS 

Google Scholar 
Hellmich, C., Moore, J. A., Bowles, K. M. & Rushworth, S. A. Bone Marrow Senescence and the Microenvironment of Hematological Malignancies. Front Oncol. 10, 230 (2020).Article 

Google Scholar 
Sandberg, J. K., Leeansyah, E., Eller, M. A., Shacklett, B. L. & Paquin-Proulx, D. The Emerging Role of MAIT Cell Responses in Viral Infections. J. Immunol. 211, 511–517 (2023).Article 
CAS 

Google Scholar 
van Wilgenburg, B. et al. MAIT cells are activated during human viral infections. Nat. Commun. 7, 11653 (2016).Article 
ADS 

Google Scholar 
Walker, L. J., Tharmalingam, H. & Klenerman, P. The rise and fall of MAIT cells with age. Scand. J. Immunol. 80, 462–463 (2014).Article 
CAS 

Google Scholar 
Junnila, R. K., List, E. O., Berryman, D. E., Murrey, J. W. & Kopchick, J. J. The GH/IGF-1 axis in ageing and longevity. Nat. Rev. Endocrinol. 9, 366–376 (2013).Article 
CAS 

Google Scholar 
Arlt, W. Dehydroepiandrosterone and ageing. Best. Pr. Res Clin. Endocrinol. Metab. 18, 363–380 (2004).Article 
CAS 

Google Scholar 
Thomas, R., Wang, W. & Su, D. M. Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging. Immun. Ageing 17, 2 (2020).Article 

Google Scholar 
Ahmed, A. S., Sheng, M. H., Wasnik, S., Baylink, D. J. & Lau, K. W. Effect of aging on stem cells. World J. Exp. Med. 7, 1–10 (2017).Article 

Google Scholar 
Sharon, E. et al. Genetic variation in MHC proteins is associated with T cell receptor expression biases. Nat. Genet 48, 995–1002 (2016).Article 
CAS 

Google Scholar 
Freitas-Simoes, T. M., Ros, E. & Sala-Vila, A. Nutrients, foods, dietary patterns and telomere length: Update of epidemiological studies and randomized trials. Metabolism 65, 406–415 (2016).Article 
CAS 

Google Scholar 
Oblak, L., van der Zaag, J., Higgins-Chen, A. T., Levine, M. E. & Boks, M. P. A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration. Ageing Res Rev. 69, 101348 (2021).Article 
CAS 

Google Scholar 
Ridout, K. K. et al. Early life adversity and telomere length: a meta-analysis. Mol. Psychiatry 23, 858–871 (2018).Article 
CAS 

Google Scholar 
Ryan, J., Wrigglesworth, J., Loong, J., Fransquet, P. D. & Woods, R. L. A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age. J. Gerontol. A Biol. Sci. Med Sci. 75, 481–494 (2020).Article 
CAS 

Google Scholar 
Choy, C. et al. SARS-CoV-2 infection establishes a stable and age-independent CD8(+) T cell response against a dominant nucleocapsid epitope using restricted T cell receptors. Nat. Commun. 14, 6725 (2023).Article 
ADS 
CAS 

Google Scholar 
Boulouis, C. et al. MAIT cell compartment characteristics are associated with the immune response magnitude to the BNT162b2 mRNA anti-SARS-CoV-2 vaccine. Mol. Med. 28, 54 (2022).Article 
CAS 

Google Scholar 
Wu, R., Sun, F., Zhang, W., Ren, J. & Liu, G. H. Targeting aging and age-related diseases with vaccines. Nat. Aging 4, 464–482 (2024).Article 

Google Scholar 
Zhang, H., Zhan, X. & Li, B. GIANA allows computationally-efficient TCR clustering and multi-disease repertoire classification by isometric transformation. Nat. Commun. 12, 4699 (2021).Article 
ADS 
CAS 

Google Scholar 
Dash, P. et al. Quantifiable predictive features define epitope-specific T cell receptor repertoires. Nature 547, 89–93 (2017).Article 
ADS 
CAS 

Google Scholar 
Kuznetsova, A., Brochkoff, P. B. & Christensen, R. H. B. lmerTest Package: Tests in Linear Mixed Effects Models. J. Statistical Software 82, 1–26 (2017).