Nat. Microbiol. https://doi.org/10.1038/s41564-018-0231-6 (2018)

Millions of humans worldwide die of Mycobacterium tuberculosis (Mtb) infection each year. While CD4+ T cells are essential for control of Mtb infection, correlates of protection remain ill-defined. In Nature Microbiology, Barber and colleagues identify CD153 expressed by CD4+ T cells as being protective in Mtb infection. CD153, also known as ‘CD30 ligand’, is a member of the tumor-necrosis factor superfamily and is encoded by TNFSF8. CD4+ T cells expressing CD153 increase in number in the lung tissues of infected mice. Mice lacking CD153 exhibit higher bacterial loads in infected lungs than do wild-type mice. While mice lacking the cytokine IFN-γ fail to contain Mtb infection, neither IFN-γ nor the transcription factor T-bet is required for CD153 expression. Importantly, CD153 expression in Mtb-specific CD4+ T cells correlates with control of lung granulomas in rhesus macaques and latent infection in humans, as opposed to patients with active Mtb infection, in whom CD153 expression is lower. Thus, CD153 provides a correlate of protection against pulmonary Mtb.