Constitutive expression of 4-1BB on T cells enhances CD4+ T cell responses.
- Author:
Juyang KIM
1
;
Sun Phil CHOI
;
Soojin LA
;
Jeong Sun SEO
;
Kack Kyun KIM
;
Seok Hyun NAM
;
Byungsuk KWON
Author Information
1. The Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea. bkwon@mail.ulsan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
antigens, CD4;
antigens, differentiation;
cytokines;
T lymphocyte;
T lymphocyte, hyper-inducer;
T lymphocyte subsets
- MeSH:
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
- From:Experimental & Molecular Medicine
2003;35(6):509-517
- CountryRepublic of Korea
- Language:English
-
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.
