How persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease.
Proc Natl Acad Sci U S A
; 121(11): e2318599121, 2024 Mar 12.
Article
em En
| MEDLINE
| ID: mdl-38446856
ABSTRACT
T cells help orchestrate immune responses to pathogens, and their aberrant regulation can trigger autoimmunity. Recent studies highlight that a threshold number of T cells (a quorum) must be activated in a tissue to mount a functional immune response. These collective effects allow the T cell repertoire to respond to pathogens while suppressing autoimmunity due to circulating autoreactive T cells. Our computational studies show that increasing numbers of pathogenic peptides targeted by T cells during persistent or severe viral infections increase the probability of activating T cells that are weakly reactive to self-antigens (molecular mimicry). These T cells are easily re-activated by the self-antigens and contribute to exceeding the quorum threshold required to mount autoimmune responses. Rare peptides that activate many T cells are sampled more readily during severe/persistent infections than in acute infections, which amplifies these effects. Experiments in mice to test predictions from these mechanistic insights are suggested.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Infecção Persistente
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article