Polarization of naive CD4+ T cells toward the Th1 subset by CTLA-4 costimulation

T Kato, H Nariuchi - The Journal of Immunology, 2000 - journals.aai.org
T Kato, H Nariuchi
The Journal of Immunology, 2000journals.aai.org
In this study, we examined in vitro the role of CTLA-4 costimulation in the polarization of
naive CD4+ T cells toward the Th1 subset. When CTLA-4 costimulation was blocked by the
inclusion of anti-CTLA-4 Fab in cultures during priming of naive CD4+ T cells with anti-CD3
in the presence of splenic adherent cells, they were polarized toward the Th2 subset.
Conversely, the engagement of CTLA-4 with immobilized anti-CTLA-4 or with CD80-P815
cells polarized naive CD4+ T cells costimulated with anti-CD3 and anti-CD28 toward the …
Abstract
In this study, we examined in vitro the role of CTLA-4 costimulation in the polarization of naive CD4+ T cells toward the Th1 subset. When CTLA-4 costimulation was blocked by the inclusion of anti-CTLA-4 Fab in cultures during priming of naive CD4+ T cells with anti-CD3 in the presence of splenic adherent cells, they were polarized toward the Th2 subset. Conversely, the engagement of CTLA-4 with immobilized anti-CTLA-4 or with CD80-P815 cells polarized naive CD4+ T cells costimulated with anti-CD3 and anti-CD28 toward the Th1 subset. The CTLA-4 costimulation during priming augmented TGF-β1 mRNA accumulation in naive CD4+ T cells, and the inclusion of anti-TGF-β in cultures for priming suppressed the effect of CTLA-4 costimulation on the Th1 polarization. The addition of low doses of TGF-β1 in cultures for priming of naive CD4+ T cells enhanced the production of Th1 cytokines upon secondary stimulation, although Th2 cytokine production was not affected by the doses of TGF-β1. The CTLA-4 costimulation was also shown to suppress IL-4 production of naive CD4+ T cells upon priming. These results indicate that the costimulation against CTLA-4 drives polarization of naive CD4+ T cells toward the Th1 subset independent of IL-12 through, at least in part, the enhancement of TGF-β1 production, and it also hampers Th2 subset differentiation by affecting IL-4 production of naive CD4+ T cells.
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