Inducible down-regulation of MHC class I results in natural killer cell tolerance.
J Exp Med
; 216(1): 99-116, 2019 01 07.
Article
en En
| MEDLINE
| ID: mdl-30559128
ABSTRACT
Natural killer (NK) cells are innate lymphocytes that are thought to kill cells that down-regulate MHC class I (MHC-I) through "missing-self" recognition. NK cells from B2m-/- mice that lack surface MHC-I, however, are not autoreactive as predicted by the missing-self hypothesis. As a result, it is unclear if MHC-I down-regulation in vivo induces NK cell reactivity or tolerance to missing-self. Here, we generated a floxed B2m mouse to acutely down-regulate MHC-I in vivo in a host that normally expresses MHC-I. Global down-regulation of MHC-I induced NK cell hyporesponsiveness and tolerance to missing-self without overt missing-self reactivity. In contrast, down-regulation of MHC-I on a small fraction of hematopoietic cells triggered missing-self reactivity. Surprisingly, down-regulation of MHC-I only on CD4+ T cells predominately induced tolerance to missing-self without resetting NK cell responsiveness. In this setting, inflammation triggered substantial missing-self reactivity. These results show that MHC-I down-regulation can induce either NK cell tolerance or killing in vivo and that inflammation promotes missing-self reactivity.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
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Linfocitos T CD4-Positivos
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Regulación hacia Abajo
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Microglobulina beta-2
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Tolerancia Inmunológica
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
Macao