Dataset Information

A Key Role of CD8+ T Cells in Controlling of Tuberculosis Infection.

ABSTRACT: The main role in the control of tuberculosis infection is played by macrophages and Th1 and CD8+ T cells. The study aimed to identify the most diagnostically significant CD8+ T cell subsets in tuberculosis patients.

Methods

Peripheral blood samples from patients with clinical, radiological, and bacteriologically confirmed pulmonary tuberculosis (TB, n = 32) and healthy subjects (HC, n = 31) were collected and analyzed using 10-color flow cytometry.

Results

The frequency of the EM4 CD3+CD8+ cells was reduced in the peripheral blood of patients with pulmonary tuberculosis, while the relative and absolute number of EM1 CD3+CD8+ cells increased compared to the control group. CD57 expression was reduced in patients with pulmonary tuberculosis on EM1, EM2, and pE1 CD3+CD8+ cells, whereas the EM3 cells had a high level of CD57 expression. The relative and absolute number of Tc2 (CCR6-CXCR3-) cells in peripheral blood in patients with pulmonary tuberculosis was increased, while the frequency of Tc1 (CCR6-CXCR3+) was decreased, compared to healthy donors.

Conclusions

Patients with pulmonary tuberculosis have an abnormal CD3+CD8+ cell profile and demonstrate their impaired maturation and functional activity.

SUBMITTER: Kudryavtsev I

PROVIDER: S-EPMC10528134 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

A Key Role of CD8+ T Cells in Controlling of Tuberculosis Infection.

Kudryavtsev Igor I Zinchenko Yulia Y Serebriakova Maria M Akisheva Tatiana T Rubinstein Artem A Savchenko Andrei A Borisov Alexandr A Belenjuk Vasilij V Malkova Anna A Yablonskiy Piotr P Kudlay Dmitry D Starshinova Anna A

Diagnostics (Basel, Switzerland) 20230915 18

The main role in the control of tuberculosis infection is played by macrophages and Th1 and CD8+ T cells. The study aimed to identify the most diagnostically significant CD8+ T cell subsets in tuberculosis patients.<h4>Methods</h4>Peripheral blood samples from patients with clinical, radiological, and bacteriologically confirmed pulmonary tuberculosis (TB, n = 32) and healthy subjects (HC, n = 31) were collected and analyzed using 10-color flow cytometry.<h4>Results</h4>The frequency of the EM4 ...[more]

PMID: 37761328

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Project description:Tuberculosis (TB) is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB). The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs) is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs), take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung) to lung-draining lymph nodes (LNs) where they prime T cells to recognize Mtb. These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent-based model (ABM, labeled GranSim) describing in silico immune cell, bacterial (Mtb) and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form), lung draining lymph node (LN, site of generation of adaptive immunity) and blood (a measurable compartment). Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM), while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs). In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs) in a computational fashion into GranSim. The model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection. The main conclusion of this study is that early events after Mtb infection are critical to establishing a timely and effective response. Manipulating CD8+ and CD4+ T cell proliferation rates, as well as DC migration early on during infection can determine the difference between bacterial clearance vs. uncontrolled bacterial growth and dissemination.

Dataset Information

A Key Role of CD8+ T Cells in Controlling of Tuberculosis Infection.

Methods

Results

Conclusions

Publications

A Key Role of CD8+ T Cells in Controlling of Tuberculosis Infection.

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