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The Role of Foxp3-Expressing Regulatory T Cells and T Helpers in Immunopathogenesis of Multidrug Resistant Pulmonary Tuberculosis

DOI: 10.1155/2012/931291

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Abstract:

Subpopulation structure of regulatory T cells and T helpers of peripheral blood in patients with newly diagnosed pulmonary tuberculosis depending on the clinical form of disease and sensitivity of Mycobacterium tuberculosis to antituberculosis drugs has been analyzed in this work. It has been shown that the leading part in immune suppression at infiltrative, dissemination, and fibrosis-cavity pulmonary tuberculosis is played by natural regulatory CD4+CD25+Foxp3+-T lymphocytes. Thus we estimate increase of their number in blood by drug-resistance and drug-susceptible patients. It has been demonstrated that in patients with fibrocavernous and infiltrative form of the disease and drug-resistant pulmonary tuberculosis the number of CD4+CD25?Foxp3+-regulatory T cells was increasing. In patients with infiltrative pulmonary tuberculosis, including multidrug-resistant M. tuberculosis, an increased number of CD3+CD4+CD25? T helpers is determined by the pathogenic features of the development of the tuberculosis infection and is connected with the activation of Th1-dependent immune response. Reduction in the number of T-helpers in the blood of patients with dissemination and fibrosis-cavity pulmonary tuberculosis mediates inefficient implementation of cell-mediated protective immunity. 1. Introduction Drug-resistant pulmonary tuberculosis (DR-TB) is a case of tuberculosis caused by M. tuberculosis strains (MBTs) which are drug resistant to the effect of antituberculosis drugs (ATDs). It is supposed that drug-resistance (DR) is, above all, connected with accumulation of mutations in M. tuberculosis genes [1]. Multidrug-resistant tuberculosis (MDR-TB) is a special form of drug-resistant TB. It develops in case of resistance of M. tuberculosis at least to isoniazid and rifampicin—the two most powerful ATDs [2]. The problem of multidrug resistance of a tuberculosis causative agent to ATD in newly detected patients has lately gained global importance [3, 4]. According to the data of World Health Organization (2010), based on the information received from 114 countries around the world, primary MDR of MBT comprises about 4% from all newly detected TB cases, whereas on the territory of the CIS countries (Russia, Belarus, Ukraine, Kazakhstan, Armenia, and Azerbaijan) this indicator is 3–6 times higher [2]. Increase in morbidity of cases with primary DR-TB in patients who earlier did not receive ATD is especially alarming [5, 6]. Primary DR-TB develops as a result of primary infection by drug-resistant M. tuberculosis strains. In some regions of Russia secondary (acquired)

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