Imperial College London
Alternate

DrNesrinaImami

Faculty of Medicine, Department of Infectious Disease

Reader in Immunology
 
 
 
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Contact

 

+44 (0)20 3315 5987n.imami Website

 
 
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Location

 

I.2.8Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Malik:2023:10.1182/blood.2022018380,
author = {Malik, A and Sayed, AA and Han, P and Tan, MMH and Watt, E and Constantinescu-Bercu, A and Cocker, ATH and Khoder, A and Saputil, RC and Thorley, EV and Teklemichael, A and Ding, Y and Hart, ACJ and Zhang, H and Mitchell, WA and Imami, N and Crawley, JTB and Salles-Crawley, II and Bussel, JB and Zehnder, JL and Adams, SP and Zhang, BM and Cooper, N},
doi = {10.1182/blood.2022018380},
journal = {Blood},
pages = {2417--2429},
title = {The role of CD8+ T cell clones in immune thrombocytopenia},
url = {http://dx.doi.org/10.1182/blood.2022018380},
volume = {141},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multi-dimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterised patients with ITP and compared them to age-matched controls using immunophenotyping, next-generation sequencing of T cell receptor (TCR) genes, single-cell RNA sequencing, and functional T cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon-g, tumour necrosis factor-a, and Granzyme B defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the T cell receptor showed expanded T cell clones in patients with ITP. T cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon-g and trigger platelet activation and apoptosis through TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP.
AU  - Malik,A
AU  - Sayed,AA
AU  - Han,P
AU  - Tan,MMH
AU  - Watt,E
AU  - Constantinescu-Bercu,A
AU  - Cocker,ATH
AU  - Khoder,A
AU  - Saputil,RC
AU  - Thorley,EV
AU  - Teklemichael,A
AU  - Ding,Y
AU  - Hart,ACJ
AU  - Zhang,H
AU  - Mitchell,WA
AU  - Imami,N
AU  - Crawley,JTB
AU  - Salles-Crawley,II
AU  - Bussel,JB
AU  - Zehnder,JL
AU  - Adams,SP
AU  - Zhang,BM
AU  - Cooper,N
DO  - 10.1182/blood.2022018380
EP  - 2429
PY  - 2023///
SN  - 0006-4971
SP  - 2417
TI  - The role of CD8+ T cell clones in immune thrombocytopenia
T2  - Blood
UR  - http://dx.doi.org/10.1182/blood.2022018380
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36749920
UR  - https://ashpublications.org/blood/article/141/20/2417/494359/The-role-of-CD8-T-cell-clones-in-immune
UR  - http://hdl.handle.net/10044/1/103350
VL  - 141
ER  -
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