This study assessed the polyfunctional T cells in healthy household contacts (HHCs) and TB patients. This study also assessed the memory subsets responsible for the secretion of IFN-γ during the short-term culture with Mycobacterium tuberculosis antigens. Frequencies of CD4+IFN-γ+TNF-α+ T cells and CD8+IFN-γ+TNF-α+ T cells specific to M. tuberculosis antigens were significantly higher in TB patients compared to HHC. IFN-γ-secreting T cells, during overnight stimulation with M. tuberculosis antigens, belonged to effector memory subset with a CD45RA？CD27？ phenotype. However, the number of IFN-γ-secreting effector memory cells did not differ between HHC and TB patients. 1. Introduction Tuberculosis (TB) is a global health problem with 2 billion people infected with the causative agent Mycobacterium tuberculosis (M. tuberculosis). Of these, only 10 percent will progress to active TB disease resulting in almost 2 million deaths per year [1]. This provides compelling evidence that the human immune system is capable of controlling the pathogen. However, the precise mechanisms contributing to the loss of immune control and progression of active TB disease are not known. A better understanding of these processes is critical for the development of improved diagnostics, treatment protocols, and vaccines. It has been long recognized that Interferon gamma (IFN-γ) producing T cells provide the major effector response in TB [2–5]. However, assessment of IFN-γ producing T cells alone may not be sufficient. Further analysis of various T cell memory subsets, such as central memory and effector memory subsets, may provide some light in understanding the T cell protection in TB. T cells are able to produce multiple factors simultaneously and they are termed polyfunctional T cells. The evidence from animal and human models of chronic viral infections indicates that high levels of chronic antigen stimulation lead to functional impairment of antigen-specific T cell responses, with reduced cytokine production, cytotoxicity, and proliferative capacity [6–11]. The capacity of antigen-specific T cells to produce multiple cytokines simultaneously has been associated with superior functional capacity [12] and has been correlated with control of human chronic viral infections such as human immunodeficiency virus (HIV) [13–15] and hepatitis C virus (HCV) [16]. Moreover, polyfunctional T cells have been associated with protection against disease progression in mouse models of Leishmania major [17] and M. tuberculosis [18]. Polyfunctional T cells, which produce IFN-γ, IL-2, and TNF-α,
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