CTLA4 protects against maladaptive cytotoxicity during the differentiation of effector and follicular CD4⁺ T cells.

ABSTRACT: As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency (PAD), analysis of affected patients could yield insights into T-cell differentiation and explain how environmental exposures modify clinical phenotypes conferred by single-gene defects. CD57 marks dysfunctional T cells that have differentiated after antigenic stimulation. Indeed, while circulating CD57⁺ CD4⁺ T cells are normally rare, we found that they are increased in patients with PAD and markedly increased with CTLA4 haploinsufficiency or blockade. We performed single-cell RNA-seq analysis of matched CD57⁺ CD4⁺ T cells from blood and tonsil samples. Circulating CD57⁺ CD4⁺ T cells (CD4cyt) exhibited a cytotoxic tr

SUBMITTER: Hao Y 

PROVIDER: S-EPMC10166697 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature