Somatic mutations associate with clonal expansion of CD8+ T cells.
Sci Adv
; 10(23): eadj0787, 2024 Jun 07.
Article
in En
| MEDLINE
| ID: mdl-38848368
ABSTRACT
Somatic mutations in T cells can cause cancer but also have implications for immunological diseases and cell therapies. The mutation spectrum in nonmalignant T cells is unclear. Here, we examined somatic mutations in CD4+ and CD8+ T cells from 90 patients with hematological and immunological disorders and used T cell receptor (TCR) and single-cell sequencing to link mutations with T cell expansions and phenotypes. CD8+ cells had a higher mutation burden than CD4+ cells. Notably, the biggest variant allele frequency (VAF) of non-synonymous variants was higher than synonymous variants in CD8+ T cells, indicating non-random occurrence. The non-synonymous VAF in CD8+ T cells strongly correlated with the TCR frequency, but not age. We identified mutations in pathways essential for T cell function and often affected lymphoid neoplasia. Single-cell sequencing revealed cytotoxic TEMRA phenotypes of mutated T cells. Our findings suggest that somatic mutations contribute to CD8+ T cell expansions without malignant transformation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Antigen, T-Cell
/
CD8-Positive T-Lymphocytes
/
Mutation
Limits:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Sci Adv
Year:
2024
Type:
Article
Affiliation country:
Finland