Constitutive expression of 4-1BB on T cells enhances CD4+ T cell responses.
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.
Kim
Juyang
J
The Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea.
Choi
Sun Phil
SP
La
Soojin
S
Seo
Jeong-Sun
JS
Kim
Kack Kyun
KK
Nam
Seok Hyun
SH
Kwon
Byungsuk
B
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division; D019070:Cell Lineage; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D000906:Antibodies; D015703:Antigens, CD; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9