Enhanced CD4+ T cell proliferation and Th2 cytokine production in DR6-deficient mice.
We have found that DR6, a member of the TNF receptor family, is highly expressed in resting T cells and downregulated in activated T cells. DR6-targeted mutant mice were generated and showed normal development. However, DR6(-/-) CD4(+) T cells hyperproliferated in response to TCR-mediated stimulation and protein antigen challenge. Activated DR6(-/-) CD4(+) T cells exhibited upregulated CD25 expression and enhanced proliferation in response to exogenous IL-2 stimulation. In addition, increased CD28 and reduced CTLA-4 expression were observed in these cells. Enhanced Th2 cytokine production by activated DR6(-/-) CD4(+) T cells was associated with the increased transcription factor NF-ATc in nuclei. DR6, therefore, functions as a regulatory receptor for mediating CD4(+) T cell activation and maintaining proper immune responses.
Liu
J
J
Department of Bio-Research Technologies and Proteins, Eli Lilly and Company, Indianapolis, IN 46285, USA.
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Glasebrook
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Fox
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Solenberg
P J
PJ
Zhang
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Song
H Y
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Yang
D D
DD
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D018796:Immunoconjugates; D008213:Lymphocyte Activation; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2 / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D018796:Immunoconjugates; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; C485251:Tnfrsf21 protein, mouse; D014157:Transcription Factors; D000069594:Abatacept; D004247:DNA