Liver transplant recipient sera derived soluble HLA mediates allele specific CTL apoptosis.
Transplantation
; 69(1): 157-62, 2000 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-10653395
ABSTRACT
BACKGROUND:
Significant levels of donor soluble human leukocyte antigen (HLA) class I (sHLA) are present in patients after transplants. We investigated the possibility that sHLA may inhibit cytolytic T lymphocyte (CTL) activity by inducing apoptosis of the CTL, thereby serving as a mechanism for specific tolerance.METHODS:
sHLA-A2 and A3 were isolated from the sera of liver transplant recipients by affinity chromatography. T cell bulk lines directed against HLA-A2 and HLA-A3 were generated by stimulation with HLA-A2, A3+ peripheral blood leukocytes and B-lymphoblastoid cells. Induction of T cell apoptosis by sHLA was analyzed by adding sHLA to allospecific CTL 4 or for 24 hr before flow cytometric analysis of propidium iodide and fluorescein isothiocyanate-conjugated annexin V stained cells. T cell receptor (TCR) engagement by sHLA was demonstrated using a monoclonal antibody specific for the TCR.RESULTS:
sHLA-A3 inhibited CTL activity of a HLA-A3 T cell line by 53%, whereas sHLA-A2 had no effect. sHLA-A3 also increased T cell death by 77% over the control, whereas sHLA-A2 had no significant effect. However, sHLA-A2 induced 21% apoptosis of an anti-HLA-A2 T cell line, whereas sHLA-A3 caused only 3% apoptosis. The antibody complexed form of sHLA was ineffective in the induction of apoptosis. Preincubation of the T cells with anti-T cell receptor monoclonal antibody protected the T cells from sHLA-induced apoptosis, indicating that sHLA-TCR engagement is necessary for this process to occur.CONCLUSION:
TCR-mediated apoptosis of alloreactive CTL may serve as a mechanism by which sHLA can modulate the immune response.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
/
Antígeno HLA-A2
/
Antígeno HLA-A3
/
Trasplante de Hígado
/
Apoptosis
/
Alelos
Límite:
Humans
Idioma:
En
Revista:
Transplantation
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos