scholarly journals Mechanisms shaping the naïve T cell repertoire in the elderly — Thymic involution or peripheral homeostatic proliferation?

2014 ◽  
Vol 54 ◽  
pp. 71-74 ◽  
Author(s):  
Qian Qi ◽  
David W. Zhang ◽  
Cornelia M. Weyand ◽  
Jörg J. Goronzy
2021 ◽  
Vol 12 ◽  
Author(s):  
Rami Bechara ◽  
Alexia Feray ◽  
Marc Pallardy

Allergic reactions to drugs and chemicals are mediated by an adaptive immune response involving specific T cells. During thymic selection, T cells that have not yet encountered their cognate antigen are considered naive T cells. Due to the artificial nature of drug/chemical-T-cell epitopes, it is not clear whether thymic selection of drug/chemical-specific T cells is a common phenomenon or remains limited to few donors or simply does not exist, suggesting T-cell receptor (TCR) cross-reactivity with other antigens. Selection of drug/chemical-specific T cells could be a relatively rare event accounting for the low occurrence of drug allergy. On the other hand, a large T-cell repertoire found in multiple donors would underline the potential of a drug/chemical to be recognized by many donors. Recent observations raise the hypothesis that not only the drug/chemical, but also parts of the haptenated protein or peptides may constitute the important structural determinants for antigen recognition by the TCR. These observations may also suggest that in the case of drug/chemical allergy, the T-cell repertoire results from particular properties of certain TCR to recognize hapten-modified peptides without need for previous thymic selection. The aim of this review is to address the existence and the role of a naive T-cell repertoire in drug and chemical allergy. Understanding this role has the potential to reveal efficient strategies not only for allergy diagnosis but also for prediction of the immunogenic potential of new chemicals.


2010 ◽  
Vol 265 (3) ◽  
pp. 396-410 ◽  
Author(s):  
Emily R. Stirk ◽  
Grant Lythe ◽  
Hugo A. van den Berg ◽  
Carmen Molina-París

2010 ◽  
Vol 107 (45) ◽  
pp. 19414-19419 ◽  
Author(s):  
M. F. Quigley ◽  
H. Y. Greenaway ◽  
V. Venturi ◽  
R. Lindsay ◽  
K. M. Quinn ◽  
...  

2011 ◽  
Vol 186 (5) ◽  
pp. 2970-2977 ◽  
Author(s):  
Maryam Yassai ◽  
Dmitry Bosenko ◽  
Melissa Unruh ◽  
Gregory Zacharias ◽  
Erica Reed ◽  
...  

2013 ◽  
Vol 43 (11) ◽  
pp. 3038-3050 ◽  
Author(s):  
Pleun Hombrink ◽  
Yotam Raz ◽  
Michel G. D. Kester ◽  
Renate de Boer ◽  
Bianca Weißbrich ◽  
...  

2018 ◽  
Vol 202 (2) ◽  
pp. 476-483 ◽  
Author(s):  
Paul Lindau ◽  
Rithun Mukherjee ◽  
Miriam V. Gutschow ◽  
Marissa Vignali ◽  
Edus H. Warren ◽  
...  

2020 ◽  
Vol 49 (3) ◽  
pp. 368-373 ◽  
Author(s):  
David B Bartlett ◽  
Niharika A Duggal

Abstract Introduction ageing is accompanied by impairments in immune responses due to remodelling of the immune system (immunesenescence). Additionally, a decline in habitual physical activity has been reported in older adults. We have recently published that specific features of immunesenescence, such as thymic involution and naïve/memory T-cell ratio, are prevented by maintenance of a high level of physical activity. This study compares immune ageing between sedentary and physically active older adults. Methods a cross-sectional study recruited 211 healthy older adults (60–79 years) and assessed their physical activity levels using an actigraph. We compared T- and B-cell immune parameters between relatively sedentary (n = 25) taking 2,000–4,500 steps/day and more physically active older adults (n = 25) taking 10,500–15,000 steps/day. Results we found a higher frequency of naïve CD4 (P = 0.01) and CD8 (P = 0.02) and a lower frequency of memory CD4 cells (P = 0.01) and CD8 (P = 0.04) T cells in the physically active group compared with the sedentary group. Elevated serum IL7 (P = 0.03) and IL15 (P = 0.003), cytokines that play an essential role in T-cell survival, were seen in the physically active group. Interestingly, a positive association was observed between IL15 levels and peripheral CD4 naïve T-cell frequency (P = 0.023). Discussion we conclude that a moderate level of physical activity may be required to give a very broad suppression of immune ageing, though 10,500–15,000 steps/day has a beneficial effect on the naïve T-cell pool.


immuneACCESS ◽  
2019 ◽  
Author(s):  
P Lindau ◽  
R Mukherjee ◽  
MV Gutschow ◽  
M Vignali ◽  
EH Warren ◽  
...  

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Wan-Lin Lo ◽  
Benjamin D Solomon ◽  
David L Donermeyer ◽  
Chyi-Song Hsieh ◽  
Paul M Allen

Naive T cell precursor frequency determines the magnitude of immunodominance. While a broad T cell repertoire requires diverse positively selecting self-peptides, how a single positively selecting ligand influences naive T cell precursor frequency remains undefined. We generated a transgenic mouse expressing a naturally occurring self-peptide, gp250, that positively selects an MCC-specific TCR, AND, as the only MHC class II I-Ek ligand to study the MCC highly organized immunodominance hierarchy. The single gp250/I-Ek ligand greatly enhanced MCC-tetramer+ CD4+ T cells, and skewed MCC-tetramer+ population toward V11α+Vβ3+, a major TCR pair in MCC-specific immunodominance. The gp250-selected V11α+Vβ3+ CD4+ T cells had a significantly increased frequency of conserved MCC-preferred CDR3 features. Our studies establish a direct and causal relationship between a selecting self-peptide and the specificity of the selected TCRs. Thus, an immunodominant T cell response can be due to a dominant positively selecting self-peptide.


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