Low‐affinity <scp>TCR</scp> engagement drives <scp>IL</scp>‐2‐dependent post‐thymic maintenance of naive <scp>CD</scp>4+ T cells in aged humans

Geest, Kornelis S M van der; Abdulahad, Wayel H.; Teteloshvili, Nato; Tete, Sarah M.; Peters, Jorieke H.; Horst, G.; Lorencetti, Pedro G.; Bos, Nicolaas A.; Lambeck, Annechien J. A.; Roozendaal, Caroline; Kroesen, Bart-Jan; Koenen, Hans J. P. M.; Joosten, Irma; Brouwer, Elisabeth; Boots, Annemieke M. H.

doi:10.1111/acel.12353

Cited by 24 publications

(15 citation statements)

References 44 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This demonstrates that after neonatal thymectomy, CD31 + T cells undergo differentiation toward CD31 -cells without the loss of CD31, supporting the observed reduction in IL-8 production and calcium flux of naive T cells after thymectomy. The phenomenon of partial differentiation of naive T cells in aging has also been suggested based on differential expression of miRNAs (miR-181a, miR146a, and miR-21) (27) and CD25 expression on naive CD4 + T cells (33). Hence, with neonatal thymectomy and with aging, naive T cells may acquire features of memory cells with maintenance of their naive phenotype.…”

Section: Discussionmentioning

confidence: 99%

Neonatal thymectomy reveals differentiation and plasticity within human naive T cells

Broek¹,

Delemarre²,

Janssen³

et al. 2016

Journal of Clinical Investigation

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Neonatal thymectomy reveals differentiation and plasticity within human naive T cells

Broek¹,

Delemarre²,

Janssen³

et al. 2016

Journal of Clinical Investigation

View full text Add to dashboard Cite

“…The consistent association found between high numbers ofCD4 naïve and the post thymically expanded CD4 + CD45RA + CD25 dim cells and a higher ratio of these naïve cells to the memory CD4 T cell compartment with low vaccine responsiveness was unexpected, since a naïve T cell repertoire is generally accepted to be beneficial in older adults ( 9 , 11 ). Previously, the CD4 + CD45RA + CD25 dim subset was found to represent a broad and functional reservoir of naïve CD4 T cells, although some contraction in certain TCR Vβ families was observed in comparison to naïve CD4 T cells that recently left the thymus ( 52 ). Since no prior studies were available that linked the numbers of CD4 + CD45RA + CD25 dim cells to vaccine responses, our findings indicate the necessity for further research into repertoire size and functionality of these cells.…”

Section: Discussionmentioning

confidence: 99%

An Explorative Biomarker Study for Vaccine Responsiveness after a Primary Meningococcal Vaccination in Middle-Aged Adults

et al. 2018

Self Cite

View full text Add to dashboard Cite

IntroductionPrevention of infectious diseases in the elderly is essential to establish healthy aging. Yet, immunological aging impairs successful vaccination of the elderly. Predictive biomarkers for vaccine responsiveness in middle-aged adults may help to identify responders and non-responders before reaching old age. Therefore, we aimed to determine biomarkers associated with low and high responsiveness toward a primary vaccination in middle-aged adults, for which a tetravalent meningococcal vaccine was used as a model.MethodsMiddle-aged adults (50–65 years of age, N = 100), receiving a tetravalent meningococcal vaccination, were divided into low and high responders using the functional antibody titers at 28 days postvaccination. A total of 48 parameters, including absolute numbers of immune cells and serum levels of cytokines and biochemical markers, were determined prevaccination in all participants. Heat maps and multivariate redundancy analysis (RDA) were used to reveal immune phenotype characteristics and associations of the low and high responders.ResultsSeveral significant differences in prevaccination immune markers were observed between the low and high vaccine responders. Moreover, RDA analysis revealed a significant association between the prevaccination immune phenotype and vaccine responsiveness. In particular, our analysis pointed at high numbers of CD4 T cells, especially naïve CD4 and regulatory T subsets, to be associated with low vaccine responsiveness. In addition, low responders showed lower prevaccination IL-1Ra levels than high responders.ConclusionThis explorative biomarker study shows associations between the prevaccination immune phenotype and vaccine responsiveness after a primary meningococcal vaccination in middle-aged adults. Consequently, these results provide a basis for predictive biomarker discovery for vaccine responsiveness that will require validation in larger cohort studies.

show abstract

“…The tyrosine-protein kinase–like 7 receptor (encoded by PTK7 ) has been reported as a marker of RTEs within the CD31 + naive T cell subset in adults with PTK7 + CD31 + naive CD4 + T cells having a 3-fold enrichment of sjTRECs as compared with their PTK7 − CD31 + counterparts ( 7 ). We and others have shown that CD25 is expressed at higher levels in naive CD4 + T cells that have divided in the periphery and that the proportions of CD31 + CD25 + and CD31 − CD25 + naive CD4 + T cells are higher with age ( 8 , 9 ). CD31 + CD25 − naive CD4 + T cells contained the highest content of sjTRECs among the 4 naive CD4 + T cell subsets examined: a 4-fold enrichment of sjTRECs in CD31 + CD25 − naive CD4 + T cells as compared with their CD31 + CD25 + counterparts was observed, thereby identifying the CD31 + CD25 − naive CD4 + T cell subset as containing the highest proportion of RTEs in adults ( 8 ).…”

Section: Introductionmentioning

confidence: 86%

Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2

Pękalski¹,

Garćıa²,

Ferreira³

et al. 2017

JCI Insight

View full text Add to dashboard Cite

The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25− naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense. We also observed an IL-8–producing memory T cell subpopulation coexpressing CR1 and CR2 and with a gene expression signature resembling that of RTEs. The functions of CR1 and CR2 on T cells remain to be determined, but we note that CR2 is the receptor for Epstein-Barr virus, which is a cause of T cell lymphomas and a candidate environmental factor in autoimmune disease.

show abstract

Low‐affinity TCR engagement drives IL‐2‐dependent post‐thymic maintenance of naive CD4+ T cells in aged humans

Cited by 24 publications

References 44 publications

Neonatal thymectomy reveals differentiation and plasticity within human naive T cells

Neonatal thymectomy reveals differentiation and plasticity within human naive T cells

An Explorative Biomarker Study for Vaccine Responsiveness after a Primary Meningococcal Vaccination in Middle-Aged Adults

Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2

Contact Info

Product

Resources

About