Abstract
Aim. To analyze the peculiarities and mechanisms of receptor-mediated T-lymphocytes disorders in different clinical forms of pulmonary tuberculosis. Materials and м ethods. The study involved 116 patients with first diagnosed infiltrative and disseminated drug-sensitive and drug-resistant pulmonary tuberculosis. The key stages in receptor-mediated activation of T-lymphocytes, isolated from blood, after their CD3/CD28-induction in vitro with addition of intracellular transport blocker were analyzed. Their immunotyping was carried out with the method of two- and threecolor flow cytofluorometry. The obtained results were statistically analyzed. Results. The breach of extracellular and intracellular stages of T-lymphocytes activation, shown by reduction in total number of CD3- and CD28-positive cells, and CD3+CD28+IL2+, CD3+CD28+IL2–, CD3+NF-kB+, CD3+NFAT2+ lymphocytes, and increase in number of CD3+CTLA4+ cells, was identified with most of their manifestations in disseminated drug-resistant pulmonary tuberculosis. It was shown that the content of CD3+AP-1+ lymphocytes is variable in drug-resistant pulmonary tuberculosis: it increases in the infiltrative form and decreases in the disseminated form. Conclusion. The results showed different mechanisms leading to a deficiency of IL-2-positive lymphocytes and T-lymphocytopenia: from “functional reserve” exhaustion of T-cells in drug-sensitive pulmonary tuberculosis to immunosuppression under the influence of suppressive cytokines (in case of the infiltrative form) and inhibitory protein CTLA4 (in case of the disseminated form) in drug-resistant pulmonary tuberculosis.
Highlights
The results showed different mechanisms leading to a deficiency of IL-2-positive lymphocytes and T-lymphocytopenia: from “functional reserve” exhaustion of T-cells in drug-sensitive pulmonary tuberculosis to immunosuppression under the influence of suppressive cytokines (in case of the infiltrative form) and inhibitory protein CTLA4 (in case of the disseminated form) in drug-resistant pulmonary tuberculosis
Siberian State Medical University 2, Moskow Tract, Tomsk, 634050, Russian Federation
Summary
Роль нарушений рецептор-опосредованной активации Т-клеток в патогенезе иммунологической недостаточности при туберкулезе легких. Цель исследования – проанализировать особенности и механизмы нарушений рецептор-опосредованной активации Т-лимфоцитов крови при разных клинических формах туберкулеза легких. Нарушения рецептор-опосредованной активации Т-лимфоцитов при туберкулезе легких обусловливаются дефицитом CD28-костимуляции и активных форм транскрипционных факторов сигнальной трансдукции, что приводит к недостаточности секреции IL-2 и развитию Т-лимфоцитопении. Что взаимодействия между антигенпрезентирующими клетками (APC) и T-лимфоцитами являются ключевым моментом в развитии иммунного ответа на M. tuberculosis и направлены на активацию наивных Т-клеток, приводящую к их трансформации в Т-лимфоциты-хелперы (Тh) типа 1 [7]. Рецептор-опосредованный путь активации (Receptor-Mediated Pathway of Activation, RMPA) Т-клеток, в котором условно выделяют внеклеточный и внутриклеточный этапы, представляет собой индукцию наивных Т-лимфоцитов через Т-клеточный рецептор (CD3-TCR) при их непосредственном контактном взаимодействии с APC.
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