INT J TUBERC LUNG DIS 17(6):825–828 © 2013 The Union http://dx.doi.org/10.5588/ijtld.12.0361 SHORT COMMUNICATION Lymphocyte subpopulations in active tuberculosis: association with disease severity and the QFT-GIT assay L. Guglielmetti,* A. Cazzadori,* M. Conti,* F. Boccafoglio,* † A. Vella, ‡ R. Ortolani, ‡ E. Concia* * Section of Infectious Diseases, Department of Pathology and Diagnostics, Azienda Ospedaliera Universitaria Integrata, Policlinico ‘G. B. Rossi’, Verona, † Department of Pneumology, Trento Hospital, Trento, ‡ Section of Immunology, Department of Pathology and Diagnostics, Azienda Ospedaliera Universitaria Integrata, Policlinico ‘G. B. Rossi’, Verona, Italy Correspondence to: Lorenzo Guglielmetti, Unità Operativa Complessa di Malattie Infettive, Azienda Ospedaliera Universi- taria Integrata Policlinico ‘G. B. Rossi’, Piazzale Ludovico Antonio Scuro 10, 37134 Verona, Italy. Tel: (+39) 045 812 8243. Fax: (+39) 045 812 8245. e-mail: lorenzo.guglielmetti@gmail.com; Michela Conti, Unità Operativa Complessa di Malattie Infettive, Azienda Ospedaliera Universitaria Integrata, Policlinico ‘G. B. Rossi’, Piazzale Ludovico Antonio Scuro 10, 37134 Verona, Italy. Tel: (+39) 045 812 8243. Fax: (+39) 045 812 8245. e-mail: michela.conti@univr.it Article submitted 16 May 2012. Final version accepted 11 January 2013. Cell-mediated immune response plays an essential role in the pathogenesis of tuberculosis (TB). We retrospec- tively evaluated lymphocyte subpopulations in 177 ac- tive TB patients compared to 93 healthy controls, finding a relevant decrease in total lymphocytes and CD8+ cells. Conversely, activated human leukocyte antigen (HLA- DR+) and CD4+CD57+ cells were higher in the TB group. B-1a (CD5+CD19+) lymphocytes were reduced in TB subjects, particularly those with extended and cavitary pulmonary forms, suggesting increased compart- mentalisation at the infection site. QuantiFERON ® -TB Gold In-Tube positive results were associated with higher HLA-DR+CD4+ and CD4+CD57+ cells, while interferon-gamma response and total lymphocyte levels were lower in advanced pulmonary TB cases. KEY WORDS: IGRA; lymphocyte phenotyping; flow cy- tometry; interferon-gamma; Mycobacterium tuberculosis CELL-MEDIATED immune response plays an essen- tial role in the pathogenesis of tuberculosis (TB); CD4+ and, more recently, CD8+ T lymphocytes have been shown to exert an important function in con- taining Mycobacterium tuberculosis infection, which is mainly explained by the production of cytokines such as tumour necrosis factor-alpha and interferon- gamma (IFN-γ). 1 In addition, some authors have re- ported the association of CD57-positive subsets in T CD4+ and CD8+ cells with IFN-γ production and cytotoxic activity. 2 It is also widely recognised that TB patients have reduced total lymphocyte counts, with prevalent reduction of CD4+ lymphocytes and a consequent decrease in the CD4+/CD8+ ratio. 3,4 IFN-γ release assays (IGRAs) are recently devel- oped diagnostic tools that indicate a cellular immune response to M. tuberculosis and are thus considered as surrogate markers of infection; however, IGRAs cannot effectively distinguish between latent and ac- tive TB. 5 A reduced IFN-γ response to IGRAs has been reported in cases with extensive pulmonary TB. 6 In TB murine models, it has been shown that B cells and antibodies have pleiotropic activities and dis- play previously underappreciated roles: in particular, B-1a (CD19+CD5+) subsets modulate the histo- pathological pattern of pulmonary granulomatous lesions. 7 In TB patients, total numbers of B cells, CD27+ memory subset and plasmablasts have been found to be lower in pleural luid than in peripheral blood. 8 The aim of the present study was to evaluate lym- phocyte subpopulations in TB patients compared to healthy blood donors, analysing the relationship with IFN-γ release as measured by QuantiFERON ® -TB Gold In-Tube (QFT-GIT; Cellestis, Carnegie, VIC, Australia) and radiological markers of advanced disease. We compared 177 active TB patients, diagnosed by positive culture or compatible histological ind- ings associated with positive molecular biology test for M. tuberculosis, with a control group of 93 healthy blood donors. The mean age was 39.3 ± 17.9 years for TB patients and 42.5 ± 11.4 for controls, with no statistically signiicant difference between the two groups. Patients with human immunodeiciency virus infection, haematological malignancies or solid cell cancers, or undergoing immunosuppressive treatment, were not considered. Overall, 128 patients (72.3%) had pulmonary TB and 49 (27.7%) had extra- pulmonary disease. Our protocol for TB patients included micro- biological examinations, the QFT-GIT assay, the SUMMARY