Immunomodulatory effect of TCD8+ cells and memory on the in vitro microbicidal activity of mononuclear cells infected with Mycobacterium tuberculosis
Name: BRUNA GRONER PEREIRA
Type: MSc dissertation
Publication date: 15/04/2020
Advisor:
Name |
Role |
|---|---|
| RICARDO PINTO SCHUENCK | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| DANIEL CLAUDIO DE OLIVEIRA GOMES | Internal Examiner * |
| LUCAS CUNHA DIAS DE REZENDE | External Examiner * |
| RODRIGO RIBEIRO RODRIGUES | Advisor * |
Summary: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is considered the ninth leading cause of death in the world. Transmitted via aerosols, after inhalation, the bacilli lodge in the summits of the lungs and are readily recognized by alveolar macrophages and dendritic cells. In numerous cases, Mtb is able to evade the innate immune system, and the adaptive response is initiated with the generation of CD4+ and CD8+ effector cells responsible for the formation of granuloma. During TB, the presence of regulatory cells (Tregs) with immunosuppressive capacity, capable of altering the immunological dynamics, has been reported. In addition, the generation of memory cells during TB has been investigated, since already treated individuals are susceptible to a new infection. In this sense, the number of studies that aim to understand the role of regulatory cells in the control of Mtb infection and its implications is growing. For this purpose, this study proposed to evaluate the in vitro response of CD8+ cells to the virulent H37Rv strain in patients with active pulmonary tuberculosis, individuals sensitized (TST+) or not (TST-) to the tuberculin test.
In response to infection, a higher frequency of activated TCD8+ was observed in non- sensitized individuals, as well as less proliferation of TCD8+ in patients with the disease. We observed an increase in regulatory TCD8+ in sensitized individuals with the disease. We reported a higher frequency of TCD8+ of effector memory in TST- individuals. Pulmonary tuberculosis patients had a lower frequency of central memory TCD8+ cells and a higher frequency of central memory TCD8+ cells with a regulatory phenotype. Sensitized individuals exhibited an increase in the frequency of naïve TCD8+ and FOXP3+ subpopulations. The results presented here point to the presence of TCD8+ Treg cells in sensitized and TBa individuals who contribute to the reduction of the proliferative capacity of TCD8+ effector cells and consequent deficit in the generation of memory cells.
