scholarly journals BKV clearance time correlates with exhaustion state and T-cell receptor repertoire shape of BKV-specific T-cells in renal transplant patients

2019 ◽  
Author(s):  
Ulrik Stervbo ◽  
Mikalai Nienen ◽  
Benjamin JD Weist ◽  
Leon Kuchenbecker ◽  
Patrizia Wehler ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Course ◽  
Cell Receptor ◽  
Clearance Time ◽  
Transplant Patients ◽  
Receptor Repertoire ◽  
Kidney Transplant Patients ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

AbstractReactivation of the BK polyomavirus is known to lead to severe complications in kidney transplant patients. The current treatment strategy relies on decreasing the immunosuppression to allow the immune system to clear the virus. Recently, we demonstrated a clear association between the resolution of BKV reactivation and reconstitution of BKV-specific CD4+ T-cells. However, which factors determine the duration of viral infection clearance remains so far unclear. Here we apply a combination of in-depth multi-parametric flow cytometry and NGS-based CDR3 beta chain receptor repertoire analysis of BKV-specific T-cells to a cohort of 7 kidney transplant patients during the clinical course of BKV reactivation. This way we followed TCR repertoires at single clone levels and functional activity of BKV-specific T-cells during the resolution of BKV infection. The duration of BKV clearance did not depend on the number of peripheral blood BKV-specific T-cells nor on a few immunodominant BKV-specific T-cell clones. Rather, the T-cell receptor repertoire diversity and exhaustion status of BKV-specific T-cells affected the duration of viral clearance: high clonotype diversity and lack of PD1 and TIM3 exhaustion markers on BKV-specific T-cells was associated with short clearance time. Our data thus demonstrate how the diversity and the exhaustion state of the T-cells can determine the clinical course of BKV infection.

scholarly journals P083 Characterisation of T-cell receptor repertoire patterns of circulating a4b7 positive memory T cells in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S176-S177
Author(s):  
A Gamliel ◽  
L Werner ◽  
N Salamon ◽  
M Pinsker ◽  
B Weiss ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Control Subjects ◽  
Receptor Repertoire ◽  
Negative Memory ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

Abstract Background Memory T cells play an important role in mediating inflammatory responses in IBD. The integrin a4b7 is highly expressed on activated T cells, and is thought to direct homing of lymphocytes to the intestine, following its binding to MADCAM-1 expressed exclusively on intestinal endothelial cells. Since UC is characterised by oligoclonal expansion of specific T-cell clonotypes, we hypothesised that circulating memory T cells with gut-homing potential would exhibit unique T-cell receptor repertoire features. Methods Peripheral blood mononuclear cells were collected from 5 control subjects and 6 pediatric patients with active UC. Following CD3 MACS sorting cells were FACS sorted into a4b7 positive and a4b7 negative CD3+CD45RO+ memory T cells. DNA was Isolated from each subset and subjected to next-generation sequencing of the TCRB. This high-throughput platform employs massive parallel sequencing to process millions of rearranged T-cell receptor (TCR) products simultaneously, and permits an in-depth analysis of individual TCRs at the nucleotide level. Comparisons of different indices of diversity, CDR3 length and clonal biochemical characteristics were performed between a4b7 positive and a4b7 negative populations for each subject, and between controls and UC patients. Results PBMCs were isolated from active UC patients during endoscopic assessment. Four patients had a Mayo endoscopic score of 2, and two patients had a score of 1. Only one patient was treated with an immunosuppressive medication (azathioprine), and five out of six patients were treated with 5ASAs. Percentages of memory T cells (43.8 ± 12.3% vs. 32.2 ± 13.1%, p = 0.17) and a4b7 positive T cells (33.6 ± 15.7% vs. 36.0 ± 17.6%, p = 0.81) were comparable between controls and UC patients. Interestingly, a4b7 positive memory T cells displayed a polyclonal distribution, in both control subjects and in UC patients, without expansion of specific clones. Different indices of diversity, including shanon’s H, clonality index and entropy, were similar among controls and patients, both for a4b7 positive and a4b7 negative populations. Finally, clonal overlap between a4b7 positive and a4b7 negative memory T cells, for each subject was high, ranging between 30–50% for controls and 27–48% for UC patients. Conclusion a4b7 expressing memory T cells exhibited a polyclonal repertoire in both control subjects and patients with active UC, with high rates of overlap with a4b7 negative memory T cells. Our study, along with additional recent reports, challenge the dogma of the importance of a4b7 expression for T-cell migration to the gut, and may suggest that vedolizumab’s suppresses intestinal inflammation by blocking the trafficking of innate immune subsets.

T-cell receptor repertoire of circulating gamma delta T-cells in Takayasu's arteritis

2006 ◽  
Vol 118 (2-3) ◽  
pp. 243-249 ◽  
Author(s):  
Sunil Kumar Chauhan ◽  
Naresh Kumar Tripathy ◽  
Nakul Sinha ◽  
Soniya Nityanand
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Takayasu’S Arteritis ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

Antigen-induced apoptosis in developing t cells: a mechanism for negative selection of the t cell receptor repertoire*

1989 ◽  
Vol 19 (11) ◽  
pp. 2175-2177 ◽  
Author(s):  
Eric J. Jenkinson ◽  
Rosetta Kingston ◽  
Christopher A. Smith ◽  
Gwynn T. Williams ◽  
John J. T. Owen
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Negative Selection ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
Induced Apoptosis ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire ◽  
Selection Of

T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire

2008 ◽  
Vol 43 (3) ◽  
pp. 229-237 ◽  
Author(s):  
Andrea Rossmann ◽  
Blair Henderson ◽  
Bettina Heidecker ◽  
Ruediger Seiler ◽  
Gustav Fraedrich ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
Atherosclerotic Lesions ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

scholarly journals The Role of the Thymus and Recent Thymic Migrants in the Maintenance of the Adult Peripheral Lymphocyte Pool

1998 ◽  
Vol 187 (11) ◽  
pp. 1839-1848 ◽  
Author(s):  
S.P. Berzins ◽  
R.L. Boyd ◽  
J.F.A.P. Miller
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Export Ratio ◽  
Receptor Repertoire ◽  
Cell Pool ◽  
Peripheral T Cells ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. Using neonatal thymi grafted under the kidney capsule, we found that irrespective of whether the pool was oversupplied (by thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export rate was constant from both the host and graft thymus, and the periphery remained constant in size. Recent thymic emigrants (RTE) were also tracked to determine the extent of their acceptance into the T cell pool of a normal mouse. As a population, RTE are phenotypically mature, but were distinct from resident T cells in the periphery, being released in a CD4/CD8 ratio approximately twice that of established peripheral T cells. This export ratio is similar to that of T cells in the mature thymic compartment, but soon after entry into the periphery, the ratio falls, indicating separate thymic and peripheral regulation of the CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery, causing displacement of resident T cells, thus maintaining the size of the peripheral pool. Although not vital for the maintenance of a functional T cell pool, the acceptance of RTE in a “full” peripheral pool would ensure that the T cell receptor repertoire is kept diverse and that the T cell population encompasses a broad range of naive as well as memory T cells.

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