Divergent fates of antigen-specific CD8+ T cell clones in mice with acute leukemia.
Cell Rep
; 37(6): 109991, 2021 11 09.
Article
en En
| MEDLINE
| ID: mdl-34758311
ABSTRACT
The existence of a dysfunctional CD8+ T cell state in cancer is well established. However, the degree to which CD8+ T cell fates are influenced by the context in which they encounter cognate tumor antigen is less clear. We previously demonstrated that CD8+ T cells reactive to a model leukemia antigen were deleted by antigen cross-presenting type 1 conventional dendritic cells (cDC1s). Here, through a study of T cell receptor (TCR) transgenic CD8+ T cells (TCRTg101) reactive to a native C1498 leukemia cell antigen, we uncover a different mode of T cell tolerance in which TCRTg101 undergo progressive expansion and differentiation into an exhausted state. Antigen encounter by TCRTg101 requires leukemia cell major histocompatibility complex (MHC)-I expression and is independent of DCs, implying that leukemia cells directly mediate the exhausted TCRTg101 phenotype. Collectively, our data reveal that leukemia antigens are presented to CD8+ T cells via discrete pathways, leading to distinct tolerant states.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Receptores de Antígenos de Linfocitos T
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Leucemia Experimental
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Presentación de Antígeno
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Linfocitos T CD8-positivos
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Tolerancia Inmunológica
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos