scholarly journals Hsp90 inhibition ameliorates CD4+T cell-mediated acute Graft versus Host disease in mice

2016 ◽  
Vol 4 (4) ◽  
pp. 463-473
Author(s):  
Carsten Berges ◽  
Thomas Kerkau ◽  
Sandra Werner ◽  
Nelli Wolf ◽  
Nadine Winter ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Cd4 T Cell ◽  
Hsp90 Inhibition ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals CD4+ T-cell reconstitution predicts Survival Outcomes after acute Graft-versus-Host-Disease; a dual center validation

Blood ◽  
2020 ◽  
Author(s):  
Coco de Koning ◽  
Susan Prockop ◽  
Ichelle van Roessel ◽  
Nancy A Kernan ◽  
Elizabeth Klein ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Cd4 T Cell ◽  
Cancer Center ◽  
Cell Recovery ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Reconstitution ◽  
Acute Graft

Acute Graft-versus-Host-Disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). We previously showed that early CD4+ T-cell reconstitution (CD4+IR) predicts survival after HCT. Here, we studied the relation between CD4+ IR and survival in patients who developed aGvHD. Pediatric patients receiving their first allogeneic HCT at the UMC Utrecht / Princess Máxima Center (UMC/PMC) or Memorial Sloan Kettering Cancer Center (MSK), were included. Primary outcomes were non-relapse mortality (NRM) and overall survival (OS), stratified for aGvHD and CD4+IR; defined as ³50 CD4+ T-cells/uL within 100 days after HCT, or prior to aGvHD onset. Multivariate and time-to-event Cox Proportional Hazard models were applied. 591 Patients (N= 276 UMC/PMC; N= 315 MSK) were included. NRM in patients with aGvHD grade III-IV with or without CD4+IR within 100 days after HCT was 30% vs 80% (p=0.02) at UMC/PMC and 5% vs 67% (p=0.02) at MSK. This associated with lower OS without CD4+IR; 61% vs. 20% (p=0.04) at UMC/PMC, and 75% vs. 33% (p=0.12) at MSK. Inadequate CD4+IR prior to aGvHD onset associates with significantly higher NRM; 74% vs 12% (p<0.001), and inferior OS; 24% vs 78% (p<0.001). In this retrospective analysis we demonstratethat early CD4+ IR, a simple and robust markerpredictive of outcomes after HCT,associates with survival after moderate to severe aGvHD.These associations need to be confirmed in a prospective manner but suggest that strategies to improve T-cell recovery after HCT may influence survival in patients developing aGvHD.

scholarly journals Identification of a Coordinated CD8 and CD4 T Cell Response Directed Against Mismatched HLA Class I Causing Severe Acute Graft-versus-Host Disease

2012 ◽  
Vol 18 (2) ◽  
pp. 210-219 ◽  
Author(s):  
Avital L. Amir ◽  
Renate S. Hagedoorn ◽  
Simone A.P. van Luxemburg-Heijs ◽  
Erik W.A. Marijt ◽  
Alwine B. Kruisselbrink ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Cell Response ◽  
Hla Class I ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Class I ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Adequate CD4+ T-cell reconstitution enhances survival probability after acute graft-versus-host-disease

Cytotherapy ◽  
2019 ◽  
Vol 21 (5) ◽  
pp. S53
Author(s):  
J. Boelens ◽  
C. Szanto ◽  
J. Langenhorst ◽  
C. Lindemans ◽  
S. Nierkens ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Survival Probability ◽  
Cd4 T Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Reconstitution ◽  
Acute Graft

scholarly journals Nrf2 is a Critical Mediator of CD4 T Cell-Induced Acute Graft-Versus-Host Disease

2018 ◽  
Vol 24 (3) ◽  
pp. S175-S176
Author(s):  
Jennifer J. Tsai ◽  
Enrico Velardi ◽  
Yusuke Shono ◽  
Kimon Argyropoulos ◽  
Odette M. Smith ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Cd4 T Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals In vivo T-cell clonal amplification at time of acute graft-versus-host disease

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2815-2820 ◽  
Author(s):  
PY Dietrich ◽  
A Caignard ◽  
A Lim ◽  
V Chung ◽  
JL Pico ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Donor Blood ◽  
Host Disease ◽  
Graft Versus Host ◽  
Junctional Region ◽  
Run Off ◽  
Pcr Products ◽  
Acute Graft

In a series of patients transplanted with HLA-matched allogeneic bone marrow grafts (alloBMT), we previously showed that a few T-cell receptor (TCR) V alpha and V beta gene segment transcripts were overexpressed in skin compared with blood at the time of acute graft- versus-host disease (aGVHD). Here, in one selected patient with overexpressed V beta 16 and V alpha 11 transcripts in skin, we analyzed the junctional variability of these transcripts in donor blood, patient blood, and skin collected at aGVHD onset. A unique junctional region sequence accounted for 81% of in frame V beta 16 transcripts (13 of 16) in skin and 59% (13 of 22) in patient blood. Similarly, two recurrent junctional region sequences were found in skin V alpha 11 transcripts, one accounting for 66% (21 of 32) and the other for 16% (5 of 32). These recurrences were also found in patient blood (36% and 15% of V alpha 11 transcripts, respectively). To extend our analysis, a polymerase chain reaction (PCR)-based method was used to precisely determine TCR beta transcript length in run-off reactions using uncloned bulk cDNA samples. All V beta-C beta PCR products analyzed in donor blood, as well as the majority of those analyzed in patient blood, included transcripts with highly diverse junctional region sizes. As expected from the sequence data, most V beta 16-C beta PCR products in skin and patient blood were of the same size (ie, same junctional region). In addition, V beta 3, V beta 5, and V beta 17 transcripts in skin were shown to display highly restricted size variability. The clonality of the V beta 16-C beta and V beta 17-C beta transcripts was further supported by the results of run-off reactions using 13 J beta specific primers. We have identified several recurrent TCR transcripts in skin, some of them also present in patient blood. These data support the view that several T-cell subpopulations are clonally expanded in vivo at the time of aGVHD onset in this case of related HLA-matched alloBMT.

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