The responses of specific immune cells, CD4+ T cells, are impaired with age due to the reduced expression of a microRNA which helps regulates the phosphatase DUSP6, important for fine-tuning T cell sensitivity to antigen. The findings, published online this week in Nature Medicine, suggest that DUSP6 could be a target to improve T cell immune responses in the elderly.
In people, T cell function declines with age, reducing protection from vaccines and increasing susceptibility to infection, but it is unclear how the impaired response of CD4+ T cells occurs.
Jorg Goronzy and colleagues show that CD4+ T cells from elderly individuals are less able to respond to antigens at low dose or of low affinity compared to CD4+ T cells from younger people. This reduced sensitivity to T cell receptor signaling was associated with decreased expression of miR-181a and increased expression of one of its targets, DUSP6; both have been previously linked to T cell receptor signaling potency. The authors found that inhibition of DUSP6 expression or function ameliorated responses of CD4+ T cells from older individuals, suggesting that targeting this pathway might improve vaccine responses in this population.