Mycobacterium tuberculosis-specific CD4 T cells expressing CD153 inversely associate with bacterial load and disease severity in human tuberculosis

Recent data from mice and non-human primate models of tuberculosis suggested that CD153, a TNF super family member, plays an important role inMycobacterium tuberculosis(Mtb) control. However, this molecule has not been comprehensively evaluated in humans. Here, we show that the proportion of Mtb-specific CD4 T cells expressing CD153 was significantly reduced in active TB patients compared to latently infected persons. Importantly, the CD153+ Mtb-specific CD4 response inversely correlated with lung bacterial load, inferred by Xpert cycle threshold, irrespective of HIV status. Antitubercular treatment partially restored CD153 expression on Mtb-specific CD4 T cells. This is the first report of a subset of Mtb-specific CD4 T cells showing strong negative correlation with bacterial burden. Building on substantial evidence from animal models implicating CD153 as a mediator of host protection, our findings suggest it may play a similar role in humans and its measurement may be useful to evaluate TB vaccine efficacy.

Automated summary

Recent data suggests that CD153 plays a crucial role in controlling Mycobacterium tuberculosis, showing reduced expression in active TB patients compared to latently infected individuals. The expression of CD153 on Mtb-specific CD4 T cells inversely correlates with lung bacterial load and can be partially restored by antitubercular treatment, indicating its potential as a marker for evaluating TB vaccine efficacy in humans.