Exp Mol Med.
2003 Dec;35(6):509-517.
Constitutive expression of 4-1BB on T cells enhances CD4+ T cell responses
- Affiliations
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- 1The Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea. bkwon@mail.ulsan.ac.kr
- 2Department of Biological Sciences, Ajou University, Suwon, Gyeonggi-do 442-749, Korea.
- 3Department of Biochemistry, College of Medicine, Seoul National University, Seoul 110-799, Korea.
- 4Deparment of Oral Microbiology, College of Dentistry, Seoul National University, Seoul 110-799, Korea.
- 5Department of Microbiology and Genetic Engineering, University of Ulsan, Ulsan 680-749, Korea.
- 6The Xenotransplantation Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea.
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.
Keyword
MeSH Terms
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Animals
Antibodies/immunology
Antigens, CD
Antigens, CD137
CD4-Positive T-Lymphocytes/cytology/*immunology/*metabolism
Cell Division
Cell Lineage
Dermatitis, Contact/genetics/immunology
Flow Cytometry
Gene Expression
Mice
Mice, Transgenic
Receptors, Nerve Growth Factor/*genetics/*metabolism
Receptors, Tumor Necrosis Factor/*genetics/*metabolism
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