Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8 + T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8 + T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8 + T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8 + T cells in LTBI subjects were mostly T EMRA cells (CD45RA + CCR7 − ), coexpressing 2B4 and CD160, and in TB patients were mostly T EM cells (CD45RA − CCR7 − ), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8 + T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8 + T cells expressed perforin and granulysin. Finally, Mtb-specific CD8 + T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8 + T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8 + T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.Keywords: Active TB disease r Cytotoxicity r Functional profile r Latent Mtb infection r Mtb-specific CD8 + T cells Additional supporting information may be found in the online version of this article at the publisher's web-site Eur. J. Immunol. 2013Immunol. . 43: 1568Immunol. -1577 Immunity to infection 1569 IntroductionOne-third of the world's population is believed to be latently infected with Mycobacterium tuberculosis (Mtb) and two million people die of tuberculosis (TB) every year [1], thus underscoring the tremendous need for protective vaccines, new diagnostic tools, and medications. T lymphocytes are thought to play an important role in the control of TB and Mtb may reactivate under certain conditions of immunodeficiency such as in elderly or secondary to coinfection with HIV or to immunosuppressive therapy [2,3]. Several studies have underscored the essential role of CD4 + T cells in protection against Mtb, since CD4 + T-cell depletion is also associated with Mtb reactivation in HIV-infected individuals [4] and uncontrolled bacilli growth [5,6]. The protective Mtb-specific CD4 + T-cell response is considered to be a typical T H 1 response with CD4 + T cells producing cytokines such as IFN-γ or TNF-α that contribute to the recruitment of monocytes and granulocytes and activate the antimicrobial activity of macrophages [7,8]. Of interest, we recently demonstrated that Mtb-specific CD4 + T-cell responses were functionally different in patients with active TB disease as compared with those in subjects with latent Mtb infection (LTBI) [9]. Several studies also suggested a role of T H 17 cells in the con...

By combining quercetin with doxorubicin, an increase in doxorubicin effects was obtained specifically in the highly invasive breast cancer cells, while in non-tumoral cells quercetin reduced doxorubicin cytotoxic side effects. Thus, quercetin associated with doxorubicin demonstrated very promising properties for developing chemotherapeutics combinations for the therapy of breast cancer.

Immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. A multiparameter flow cytometry assay assessing T-cell responses specific to Mycobacterium tuberculosis and the combination of both CD4 and CD8 T-cell responses accurately discriminated between active tuberculosis and latent infection.