Abstract
4-1BB, a transmembrane molecule, member of the tumor necrosis factor receptor superfamily, is an important costimulatory molecule in the immune response, plays a key role in the clonal expansion and survival of CD8+ T cells. In this study, we investigated 4-1BB regulation of CD4+ T cell responses using 4-1BB transgenic (TG) mice that constitutively expressed 4-1BB on mature T cells. We first showed that CD4+ T cells of 4-1BB TG mice had more sustained proliferative capacity in response to TCR/4-1BB stimulation in vitro compared to WT mice. Secondly, 4-1BB TG mice exhibited a more elevated contact hypersensitivity (CHS) response mediated by CD4+ Th1 cells due to more vigorous expansion of and apoptotic inhibition of CD4+ T cells. Finally, CD4+ T cells of 4-1BB TG mice had a heightened capacity for T cell priming. Overall, our results demonstrate the involvement of 4-1BB in CD4+ Th1 cell responses by regulating the clonal expansion and survival of CD4+ T cells as seen in CD8+ T cells.
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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Kim, J., Choi, S., La, S. et al. Constitutive expression of 4-1BB on T cells enhances CD4+ T cell responses. Exp Mol Med 35, 509–517 (2003). https://doi.org/10.1038/emm.2003.66
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DOI: https://doi.org/10.1038/emm.2003.66