Targeted depletion of PD-1-expressing cells induces immune tolerance through peripheral clonal deletion.
Sci Immunol
; 9(94): eadh0085, 2024 Apr 26.
Article
en En
| MEDLINE
| ID: mdl-38669317
ABSTRACT
Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)-mediated ablation of PD-1+ cells reshaped the TCR repertoire through peripheral clonal deletion of alloreactive T cells and promoted tolerance in mouse transplantation models. In addition, by using PD-1-specific depleting antibodies, we found that antibody-mediated depletion of PD-1+ cells prevented heart transplant rejection and the development of experimental autoimmune encephalomyelitis (EAE) in humanized PD-1 mice. Thus, these data suggest that PD-1 is an attractive target for peripheral clonal deletion and induction of immune tolerance.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Supresión Clonal
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Receptor de Muerte Celular Programada 1
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Tolerancia Inmunológica
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Ratones Endogámicos C57BL
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Sci Immunol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China