High concentrations of atorvastatin reduce in-vitro function of conventional T and regulatory T cells

ABSTRACT: Regulatory T cells (Tregs ) modulate the magnitude of immune responses and possess therapeutic potential in an array of immune diseases. Statins reduce the activation and proliferation of conventional T cells (Tcons ), and they seem to up-regulate the frequency and function of Tregs . Howe...

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Autores:
Rodríguez Perea, Ana Lucía
Rojas López, Mauricio
Velilla Hernández, Paula Andrea
Tipo de recurso:
Article of investigation
Fecha de publicación:
2019
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/32160
Acceso en línea:
https://hdl.handle.net/10495/32160
Palabra clave:
Antígenos CD
Antigens, CD
Atorvastatina
Atorvastatin
Antígeno CTLA-4
CTLA-4 Antigen
Células Cultivadas
Cells, Cultured
Citocinas
Cytokines
Citometría de Flujo
Flow Cytometry
Factores de Transcripción Forkhead
Forkhead Transcription Factors
Interleucina-2
Interleukin-2
Linfocitos T Reguladores
T-Lymphocytes, Regulatory
Factor de Necrosis Tumoral alfa
Tumor Necrosis Factor-alpha
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/2.5/co/
Description
Summary:ABSTRACT: Regulatory T cells (Tregs ) modulate the magnitude of immune responses and possess therapeutic potential in an array of immune diseases. Statins reduce the activation and proliferation of conventional T cells (Tcons ), and they seem to up-regulate the frequency and function of Tregs . However, there is a lack of simultaneous evaluation of the in-vitro effect of statins on the functional profile of Tregs versus Tcons . Herein, magnetically purified Tcons and Tregs were stimulated with CD3/CD28/interleukin (IL)-2 in the presence of atorvastatin (ATV) at 1 or 10 µM. The suppressive function of Tregs , the expression of markers associated with Treg function, activation levels, cytokine production and calcium flux in both subpopulations were assessed by flow cytometry. ATV had no cytotoxic effect on T cells at the concentrations used. Interestingly, 10 µM ATV hampered the suppressive capacity of Tregs . Moreover, this higher concentration reduced the expression of forkhead box protein 3 (FoxP3), cytotoxic T lymphocyte antigen (CTLA-4) and programmed death 1 (PD-1). In Tcons , ATV at 10 µM decreased PD-1 and CD45RO expression. The expression of CD25, CD69, CD95, CD38, CD62L, CCR7 and perforin was not affected in both subpopulations or at any ATV concentrations. Remarkably, 10 µM ATV increased the percentage of tumour necrosis factor (TNF)-α-producing Tregs . Although there was a reduction of calcium flux in Tcons and Tregs , it was only significant in 10 µM ATV-treated Tcons . These results suggested that 10 µM ATV affects the cellular functions of both populations; however, this concentration particularly affected several aspects of Treg biology: its suppressive function, cytokine production and expression of Treg -specific markers.