Expansion of polyfunctional HIV-specific T cells upon stimulation with mRNA electroporated dendritic cells in the presence of immunomodulatory drugs.
J Virol
; 86(17): 9351-60, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-22718823
ABSTRACT
Recently, it has been demonstrated that disease progression during HIV infection is not determined merely by the number of HIV-specific T cells but also by their quality (J. R. Almeida, et al., J. Exp. Med. 2042473-2485, 2007; C. T. Berger, et al., J. Virol. 859334-9345, 2011; M. R. Betts, et al., Blood 1074781-4789, 2006; V. V. Ganusov, et al., J. Virol. 8510518-10528, 2011; P. Kiepiela, et al., Nat. Med. 1346-53, 2007; and F. Pereyra, et al., J. Infect. Dis. 197563-571, 2008). Therefore, strategies to specifically enhance or induce high-quality, HIV-specific T-cell responses are necessary to develop effective immune therapies. Thalidomide, lenalidomide, and pomalidomide have a strong capacity to boost immune responses and are therefore referred to as immunomodulatory drugs (IMiDs). We evaluated the effects of lenalidomide and pomalidomide on HIV-specific T cells. We found that the presence of IMiDs during in vitro T-cell stimulation with dendritic cells electroporated with Gag- or Nef-encoding mRNA resulted in higher numbers of cytokine-secreting HIV-specific CD8(+) T cells, particularly inducing polyfunctional HIV-specific CD8(+) T cells with an enhanced lytic capacity. Furthermore, CD8(+) T-cell responses were detected upon stimulation with lower antigenic peptide concentrations, and a higher number of Gag epitopes was recognized upon addition of IMiDs. Finally, IMiDs reduced the proliferation of the HIV-specific CD4(+) T cells while increasing the number of polyfunctional CD4(+) T cells. These results provide new information about the effects of IMiDs on antigen-specific T cells and suggest that these drugs increase the efficacy of immune therapies for infectious diseases and cancer.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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Infecciones por VIH
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VIH-1
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Linfocitos T CD8-positivos
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Factores Inmunológicos
Límite:
Humans
Idioma:
En
Revista:
J Virol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Bélgica