Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanism responsible for differences in disease manifestations and severity.
Clin Immunol
; 188: 94-102, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29305966
ABSTRACT
The CTLA-4 checkpoint regulates the activation of T cells. Individuals with heterozygous mutations in CTLA-4 have a complex phenotype typically characterized by antibody deficiency alongside variable autoimmunity. Despite severe disease in some individuals, others remain largely unaffected with reasons for this variation unknown. We studied a large family carrying a single point mutation in CTLA-4 leading to an amino acid change R75W and compared both unaffected with affected individuals. We measured a variety of features pertaining to T cell and CTLA-4 biology and observed that at the cellular level there was complete penetrance of CTLA-4 mutations. Accordingly, unaffected individuals were indistinguishable from those with disease in terms of level of CTLA-4 expression, percentage of Treg, upregulation of CTLA-4 upon stimulation and proliferation of CD4 T cells. We conclude that the wide variation in disease phenotype is influenced by immune variation outside of CTLA-4 biology.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Linfócitos T
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Antígenos CD28
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Antígeno CTLA-4
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article