Circulating T cell specific extracellular vesicle profiles in cardiac allograft acute cellular rejection.
Am J Transplant
; 24(3): 419-435, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38295008
ABSTRACT
There is a critical need for biomarkers of acute cellular rejection (ACR) in organ transplantation. We hypothesized that ACR leads to changes in donor-reactive T cell small extracellular vesicle (sEV) profiles in transplant recipient circulation that match the kinetics of alloreactive T cell activation. In rodent heart transplantation, circulating T cell sEV quantities (P < .0001) and their protein and mRNA cargoes showed time-specific expression of alloreactive and regulatory markers heralding early ACR in allogeneic transplant recipients but not in syngeneic transplant recipients. Next generation sequencing of their microRNA cargoes identified novel candidate biomarkers of ACR, which were validated by stem loop quantitative reverse transcription polymerase chain reaction (n = 10). Circulating T cell sEVs enriched from allogeneic transplant recipients mediated targeted cytotoxicity of donor cardiomyocytes by apoptosis assay (P < .0001). Translation of the concept and EV methodologies to clinical heart transplantation demonstrated similar upregulation of circulating T cell sEV profiles at time points of grade 2 ACR (n = 3 patients). Furthermore, T cell receptor sequencing of T cell sEV mRNA cargo demonstrated expression of T cell clones with intact complementarity determining region 3 signals. These data support the diagnostic potential of T cell sEVs as noninvasive biomarker of ACR and suggest their potential functional roles.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Linfocitos T
/
Vesículas Extracelulares
Límite:
Humans
Idioma:
En
Revista:
Am J Transplant
/
Am. j. transplant
/
American journal of transplantation
Asunto de la revista:
TRANSPLANTE
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos