Study of the Effect of the Anti-inflammatory Cytokines IL-10 and TGF-ß on the IL-15- induced Activation of Human T Cells

• Autor(a) principal: Peixoto, Hugo Filipe Abelha
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/13900
• topic: Ativação e Proliferação de Células T; Células T Cd4+ e Cd8+; Conformadores de Mhc-I Abertos e Fechados; Il-10; Il-15; Tgf-ß; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

The human immunological system is composed of multiple elements working together to protect the body against deaseases and external agents, maintaining a good health and balance. Here, we highlight the importance of T cells and their pivotal role for the correct functioning of the immunological system. Other elements of great importance are Major Histocompatibility Complex Class I (MHC-I) molecules, commonly found throughout all cells, including T cells. These molecules are best known when in their closed conformation, however, upon certain structural changes, they can adopt an open form, becoming known as open MHC-I conformers. The functions of these open conformers go far beyond common immune roles, participating in non-immunological functions and exerting an impact in several clinical and biomedical settings. Previous studies have shown that T cells can be modulated by IL-15, impacting their activation, proliferation and differentiation. However the effect of this modulation on the expression of open MHC-I conformers is thus far unknown. The influence of other cytokines widely found in the immunological system, namely IL-10 and TGF-ß, on this IL-15-induced modulation and on the expression of the same open conformers of MHC-I, is also yet to be determined. In this study, peripheral blood lymphocytes (PBL) were isolated from buffy coats of healthy donors, labelled with CFSE, and cultured for 12 days in the presence of IL-15, with the addition of IL-10 or TGF-ß in different concentrations and at different days. Cells were then labelled with several antibodies in order to differentiate between CD4+ and CD8+ and to detect open/closed MHC-I conformers. Analysis by flow cytometry was later conducted. Results clearly show that the presence of either IL-10 or TGF-ß greatly enhances the already known proliferative modulation of IL-15 on T cells, most noticeably when in combination with higher concentrations of the secondary cytokine (IL-10/TGF-ß). Moreover, this study has demonstrated a direct impact not only of IL-15, but also IL-10 and TGF-ß, on the expression of open MHC-I conformers on T cells, constituting novel discoveries. The expression of these conformers was seen to increase in the presence of IL-15, while the simultaneous presence of IL-10 and TGF-ß counterbalanced this effect, decreasing the levels of open MHC-I conformers.