Article
Regulation of T lymphocyte apoptotic markers is associated to cellactivation during the acute phase of dengue
Registro en:
CARVALHO, Amanda Torrentes et al. Regulation of T lymphocyte apoptotic markers is associated to cell activation during the acute phase of dengue. Immunobiology, v.219, n.5, p.329–340, May 2014.
0171-2985
10.1016/j.imbio.2013.11.002
Autor
Carvalho, Amanda Torrentes
Marinho, Cintia Ferreira
Pinto, Luzia Maria de Oliveira
Oliveira, Débora Batista de
Damasco, Paulo Vieira
Cunha, Rivaldo Venâncio
Souza, Luiz José de
Azeredo, Elzinandes Leal de
Kubelka, Claire Fernandes
Resumen
Dengue fever, a public health problem in Brazil, may present severe clinical manifestations as result of an increased vascular permeability and coagulation disorders. T cell activation is a critical event for an effective immune response against infection, including the production of cytokines. We aim to reveal mechanisms that modulate the virus-cell interaction, with an emphasis on cell death. Apoptosis is involved in lymphocyte homeostasis, contributes to the clearance of virus-infected cells but also may play a role in the pathogenesis. Phosphatidylserine exposure on CD8T lymphocytes from dengue patients support early apoptotic processes and loss of genomic integrity, observed by DNA fragmentation in T lymphocytes and indicating late apoptosis. These T cells express activation and cytotoxic phenotypes as revealed by CD29 and CD107a upregulation. Higher frequencies of CD95 were detected in T lymphocytes mainly in those with the cytotoxic profile (CD107a+) and lower levels of anti-apoptotic molecule Bcl-2, suggesting that both CD4+ and CD8+ T cell subsets are more susceptible to apoptosis during acute dengue. The analysis of apoptosis-related protein expression profile showed that not only molecules with pro- but also those with anti-apoptotic functions are overexpressed, indicating that survival mechanisms could be possibly protecting cells against apoptosis caused by viral, immune, oxidative and/or genotoxic stresses. These observations led us to propose that in dengue patients there is an association between T cell susceptibility to apoptosis and the activation state. The mechanisms for understanding the immunopathogenesis during dengue infection are discussed.