Frequent occurrence ofin vivo clonal expansion of CD4− CD8− T cells bearing T cell receptor αβ chains in adult humans

1993 ◽  
Vol 23 (11) ◽  
pp. 2735-2739 ◽  
Author(s):  
Yoichiro Kusunoki ◽  
Yuko Hirai ◽  
Tomonori Hayashi ◽  
Seishi Kyoizumi ◽  
Keiko Takahashi ◽  
...  
2003 ◽  
Vol 90 (08) ◽  
pp. 279-292 ◽  
Author(s):  
Takaji Matsutani ◽  
Yoshihiko Sakurai ◽  
Takeshi Yoshioka ◽  
Yuji Tsuruta ◽  
Ryuji Suzuki ◽  
...  

SummaryReplacement therapy with factor VIII (FVIII) products causes immune abnormalities in human immunodeficiency virus (HIV)-seronegative hemophilia patients. However, the question remains why an absolute increase in the number of CD8+ T-cells and diminished proliferation responses of lymphocytes to antigen stimulation in vitro occurs in HIV-seronegative hemophilia patients.To examine whether the FVIII products induce skewing of T-cell receptor (TCR) repertoires, TCR variable region α-chain and β–chain repertoires were analyzed for peripheral blood mononuclear cells (PBMCs) from 15 hemophilia patients treated with heated and/or non-heated plasma-derived FVIII concentrates and 10 age-matched healthy adults. Also, T-cell clonality was compared between these groups using complementarity-determining region 3 (CDR3) size spectratyping. The skewing of TCR repertoires was significantly greater for hemophilia patients than healthy controls. The extent of T-cell clonality was greater for hemophilia patients than the controls, indicating that clonal T-cells frequently expanded in hemophilia patients. The skew in TCR usage and clonal expansion were primarily observed in patients treated with non-heated plasma-derived products.The spectratyping and sequencing of CDR3 regions revealed that the clonal expansion of T-cells was observed for CD8+ T-cells, but not CD4+ T-cells.These results suggest that extensive expansion of CD8+ T-cells is induced by some viruses other than HIV present in FVIII preparations, and the resulting accumulation of CD8+ T-cells is responsible for changes in peripheral T-cell population in HIV-seronegative hemophilia patients.


2008 ◽  
Vol 14 (12) ◽  
pp. 1390-1395 ◽  
Author(s):  
Angel Varela-Rohena ◽  
Peter E Molloy ◽  
Steven M Dunn ◽  
Yi Li ◽  
Megan M Suhoski ◽  
...  

Hematology ◽  
2009 ◽  
Vol 14 (2) ◽  
pp. 106-110 ◽  
Author(s):  
Bo Li ◽  
Yangqiu Li ◽  
Shaohua Chen ◽  
Lijian Yang ◽  
Wei Yu ◽  
...  

Author(s):  
Christian R Schultze-Florey ◽  
Leonie Kuhlmann ◽  
Solaiman Raha ◽  
Joana Barros-Martins ◽  
Ivan Odak ◽  
...  

Donor lymphocyte infusion (DLI) is a standard of care for relapse of AML after allogeneic hematopoietic stem cell transplantation (aHSCT). Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GvL) activity after DLI. Also, there is no reliable biomarker to monitor GvL activity of the infused CD8+ T cells. Therefore, we analyzed the dynamics of CD8+ αβ T cell clones in DLI-patients. In this prospective clinical study of 29 patients, we performed deep T cell receptor β (TRB) sequencing of sorted CD8+ αβ T cells to track patients' repertoire changes in response to DLI. Upon first occurrence of GvL, longitudinal analyses revealed a preferential expansion of distinct CD8+ TRB clones (n=14). This did not occur in samples of patients without signs of GvL (n=11). Importantly, early repertoire changes 15 days after DLI predicted durable remission for the 36 months study follow-up. Furthermore, absence of clonal outgrowth of the CD8+ TRB repertoire after DLI was an early biomarker that predicted relapse at a median time of 11.2 months ahead of actual diagnosis. Additionally, unbiased sample analysis regardless of the clinical outcome revealed that patients with decreasing CD8+ TRB diversity at day 15 after DLI (n=13) had a lower relapse incidence (P=0.0040) compared to patients without clonal expansion (n=6). In conclusion, CD8+ TRB analysis may provide a reliable tool for predicting the efficacy of DLI and holds the potential to identify patients at risk for progression and relapse after DLI.


2016 ◽  
Vol 12 (11) ◽  
pp. e1006030 ◽  
Author(s):  
Aileen G. Rowan ◽  
Aviva Witkover ◽  
Anat Melamed ◽  
Yuetsu Tanaka ◽  
Lucy B. M. Cook ◽  
...  

Haematologica ◽  
2018 ◽  
Vol 104 (3) ◽  
pp. 622-631 ◽  
Author(s):  
Cornelia S. Link-Rachner ◽  
Anne Eugster ◽  
Elke Rücker-Braun ◽  
Falk Heidenreich ◽  
Uta Oelschlägel ◽  
...  

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