The C-type lectin-like receptor CD161 is expressed on lymphocytes found in human gut and liver, as well as blood, especially Natural Killer cells, T helper 17 cells and a population of unconventional T cells known as Mucosal Associated Invariant T (MAIT) cells. The association of high CD161 expression with innate T cell populations including MAIT cells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including anti-viral populations, which display a memory phenotype. These memory CD161int CD8+ T cells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterised by enhanced polyfunctionality, increased levels of cytotoxic mediators and high expression of the transcription factors T-bet and Eomesodermin. Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against Hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T cell populations in humans. Since induction of such responses represents a major aim of T cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.

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T-cell biomarkers for diagnosis of tuberculosis: candidate evaluation by a simple whole blood assay for clinical translation To the Editor: Diagnosis of pulmonary tuberculosis (TB) disease, the most common cause of death due to infection globally [1], depends on direct detection of Mycobacterium tuberculosis, typically from a sputum specimen. However, up to half of individuals with microbiologically proven TB do not have a prolonged productive cough [2], required to produce sputum. To address this challenge, investigators have identified candidate blood-based host biomarkers for TB diagnosis, based on M. tuberculosis-specific T-cell memory phenotypes, activation or cytokine expression profiles [3-9]. Such biomarkers have also shown potential as surrogates to monitor TB treatment response [3, 10]. Here, we aimed to: 1) compare the diagnostic performance of several blood-based T-cell biomarkers in TB patients and controls; 2) determine if combinations of these biomarkers improve diagnostic performance; 3) identify the minimal number of flow cytometry parameters required to distinguish active TB patients from persons with latent M. tuberculosis infection (LTBI); and 4) translate measurement of these biomarkers from peripheral blood mononuclear cells to whole blood to enable a simplified application in field studies. We enrolled 25 healthy adults with LTBI, defined by QuantiFERON-TB Gold In-Tube assay (QFT; Qiagen, Hilden, Germany), and 25 HIV-negative adults with TB disease (XpertMTB/RIF+) (Cepheid, Sunnyvale, CA, USA) from a region endemic for TB in South Africa. Blood was collected prior to treatment initiation in persons with active TB and 12-18 months later, after they were declared cured (n=19). In controls, blood was also collected at 12-18 months after enrolment (n=20). Whole blood was stimulated with whole mycobacteria (BCG, Connaught), ESAT-6/CFP-10 peptides from QFT tubes, and TB122 peptide pool [11] using a standardised protocol [12]. Cells were stained with the following antibodies: anti-CD3 (Beckman Coulter, Krefeld, Germany; clone UCHT1; ECD), anti-CD4