In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 89, No. 6 ( 2011-03-22), p. 989-999
Kurzfassung:
One of the consequences of HIV infection is a progressive loss of T cell functions, resulting in decreased cytokine secretion and proliferation and an increased sensitivity to apoptosis. Therefore, successful therapeutic vaccination approaches should aim at restoring the functionality of existing HIV-specific T cells, as well as to efficiently induce potent, HIV-specific T cells from naïve T cells. In this study, we wanted to determine the stimulatory capacity of DCs coelectroporated with mRNA encoding for different costimulatory molecules of the TNFSF, together with HIV antigen-encoding mRNA. We show that DCs electroporated with 4-1BBL can enhance the proliferation, functionality, cytokine production, and survival of HIV-specific CD8+ T cells. Furthermore, we are the first to show that a combination of 4-1BBL and CD40L overexpression on DCs dramatically enhances CD4+ and CD8+ T cell responses. Finally, we demonstrate that signaling through 4-1BB, but not through CD40, can alleviate the suppressive effect of Tregs on CD8+ T cell proliferation. Thus, the combination of 4-1BBL and CD40L enhances HIV-specific CD8+ T cell responses in a synergistic way, resulting in enhanced proliferation of CD4+ and CD8+ T cell subsets, an increased cytokine secretion, and a reduced sensitivity to Treg-mediated immune suppression.
Materialart:
Online-Ressource
ISSN:
0741-5400
,
1938-3673
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2011
ZDB Id:
2026833-6
SSG:
12
