Phenotypic changes induced by IL-15 in human CD8+ T cells in vitro

• Autor(a) principal: Ferreira, Diogo Ministro
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/5892
• topic: Células T Cd8+ "Nk-Like"; Citometria de Fluxo; Diferenciação; Il-15; Linfócitos; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Interleukin-15 (IL-15) is a type I cytokine that belongs to the common cytokine-receptor ?-chain family and that plays a role in development, homeostasis and immune functions of NK and CD8+ T cells. Recent studies have shown that IL-15 is capable of differentiating human naïve CD8+ T cells into NK-like CD8+ T cells displaying a multifunctional phenotype. NK-like CD8+ T cells constitute a subset of mainstream T lymphocytes that down-regulate expression of naïve T cell markers (e.g., CD8?, CD28) and, in contrast, express receptors previously thought to be expressed exclusively by NK cells (e.g. CD56, CD94/NKG2A, KIR, etc.). Under many different designations, these NK-like CD8+ T cells are the focus of intensive research because they not only constitute a significant proportion of circulating CD3+ T cells in healthy elderly individuals, including centenarians, but also in patients suffering from a variety of chronic inflammatory and metabolic disorders associated with aging. Regarding these data, the aim of this work was to study the effect of IL-15 on parameters of CD8+ T cell differentiation in vitro, namely expression of CD8?? receptor and NK receptors such as CD16, CD56, CD57 and CD335. In order to achieve that, blood samples from ten patients with erythrocytosis or increased levels of serum ferritin being followed at the Immunohemotherapy service of CHCB were included in the study. CD8+CD56+ T cells were obtained from peripheral blood mononuclear cells (PBMC) after magnetic cell purification, labeled with CFSE and cultured for 12 days. IL-15 was added to the cultures on days 0 and 6. The percentage of CD16+, CD56+, CD57+, CD335+ and CD8ß+ within dividing CD3+CD8+ T cells after the 12-day culture period was determined by flow cytometry. Student t-test was used to assess statistical differences in the expression of the studied receptors. Results showed that IL-15 induced a statistically significant increase in CD3+CD8+CD56+ and CD3+CD8+CD57+ T cells by day 12 when compared to day 0. In contrast, a statistically significant decrease in the percentage of CD3+CD8?+ T cells was observed at day 12 when compared to day 0. No statistical differences were observed in the percentage of CD3+CD8+CD16+ and CD3+CD8+CD335+ T cells. All together, these results suggest that IL-15, a cytokine highly expressed during chronic inflammation, may have a role in the generation of NK-like CD8+ T cells. Given the growing role of these CD8+ T cells in health and disease they may be turn up to be therapeutic targets.