Further investigations in different regions, with satisfying controls, and containing the data of mtDNA subhaplogroups are required to clarify the correlation and the underlying mechanism. Exposure to Mycobacterium tuberculosis can result in a variety of outcomes, including the absence of any clinical or laboratory evidence of infection, latent Euphorbia factor L3 infection without active disease, active pulmonary disease or active extra-pulmonary disease. Although 2 billion people worldwide are infected with Mtb, only 5�C10% of these individuals develop active disease, and the mechanisms by which most individuals resist development of active disease are still not clear. However, while by definition, individuals developing active TB exhibit a compromise in their ability to mount a protective immune response against MTB, the exact nature of this protective immune response needs to be determined. A wide range of specific and non-specific host immune responses are thought to contribute to the differential outcomes of infection and disease, although there is no unifying hypothesis to explain the differences seen. Gentamycin Sulfate circulating Tfh cells are peripheral counterparts of conventional Tfh cells, that are predominantly located in secondary lymphoid tissues. Conventional Tfh cells are CD4+T cells that express the chemokine receptor CXCR5, co-stimulatory molecules such as ICOS, PD-1, the transcription factor Bcl-6 and the cytokine, IL-21. Circulating Tfh cells similarly express CXCR5, PD-1, ICOS but do not express Bcl-6. In addition, although some studies have defined circulating human Tfh cells as all CD4 + T cells expressing CXCR5 + only, other studies have suggested that T cells can be further divided into those that are PD-1, ICOS, and/or IL-21. It is unclear whether expression of PD1, ICOS or IL-21 defines different subpopulations of Tfh cells. Nevertheless, these cells are known to promote the differentiation of memory B cells to plasma cells. Dysregulated activity of conventional and circulating Tfh cells have been found to contribute to autoimmune or immune-deficiency states in several models of human disease. In addition, circulating Tfh cells have been shown to be biomarkers of effective humoral immunity in vaccination and infectious disease studies. Finally, conventional Tfh 
cells have been shown to mediate protective immunity against tuberculosis. Thus, while the requirement for Tfh cells in animal models of TB infection is well-defined, the role of circulating Tfh cells in human TB infection and disease has not been explored. Infection with Mtb can lead to various outcomes that range from active or chronic pulmonary disease, extra-pulmonary TB and latent TB, that occurs when the initial infection is controlled but not completely eliminated. While a number of host immune mechanisms have been described to play a role in the diverging clinical manifestations of TB infection and disease, the immune mechanisms that contribute directly to disease pathogenesis are still incompletely understood. It has recently been demonstrated that CXCR5 + T cell accumulate within ectopic lymphoid structures associated with TB granulomas in humans, non-human primates and mice. These lymphoid follicles appear to be important for proper localization of T cells in the granulomas, for the optimal activation of macrophages and for protection against TB disease. Thus, while Tfh cells located within the granulomas are clearly important in the immune response to TB, the role of circulating Tfh cells in human TB infection and disease remains unexplored. The distribution of Tfh cells in TB infection and disease was studied by classifying them into 3 subsets.