Background: Recently-acquired and remotely-acquired latent tuberculosis (TB) infection (LTBI) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to active TB (ATB) in immunocompetent individuals. We aimed to evaluate the ability of cellular immune signatures which differ between ATB and LTBI, to distinguish recently from remotely acquired LTBI. Methods: Fifty-nine individuals were recruited: ATB (n=20); recent LTBI (n=19); remote LTBI (n=20). The proportion of mycobacteria-specific TNFα+IFNγ-IL-2-- secreting CD4+ T cells with a differentiated effector phenotype (TNFα-only TEFF), and the level of CD27 expression on IFNγ-producing CD4+ T cells, were detected by flow-cytometry. Results: The TNFα-only TEFF signature was significantly higher in recent compared to remote LTBI (p<0.0001), and discriminated between these groups with high sensitivity and specificity, with an area under the curve (AUC) = 0.87. Two signatures incorporating CD27 expression did not distinguish between recent and remote LTBI. Interestingly, the TNFα-only TEFF signature in recent LTBI was more similar to ATB than remote LTBI, suggesting that recent LTBI is immunologically more similar to ATB than remote LTBI. Conclusions: These findings reveal marked biological heterogeneity underlying the clinically homogeneous phenotype of LTBI, providing a rationale for immunological risk-stratification for improved targeting of LTBI treatment.