| Active CD4+ helper T cells directly stimulate CD8+ cytotoxic T lymphocyte responses in wild-type and MHC II gene knockout C57BL/6 mice and transgenic RIP-mOVA mice expressing islet beta-cell ovalbumin antigen leading to diabetes. | |
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MedLine Citation:
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PMID: 18855194 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CD4+ helper T (Th) cells play crucial role in priming, expansion and survival of CD8+ cytotoxic T lymphocytes (CTLs). However, how CD4+ Th cell's help is delivered to CD8+ T cells in vivo is still unclear. We previously demonstrated that CD4+ Th cells can acquire ovalbumin (OVA) peptide/major histocompatibility complex (pMHC I) and costimulatory CD80 by OVA-pulsed DC (DC(OVA)) stimulation, and then stimulate OVA-specific CD8+ CTL responses in C57BL/6 mice. In this study, we further investigated CD4+ Th cell's effect on stimulation of CD8 CTL responses in major histocompatibility complex (MHC II) gene knockout (KO) mice and transgenic rat insulin promoter (RIP)-mOVA mice with moderate expression of self OVA by using CD4+ Th cells or Th cells with various gene deficiency. We demonstrated that the in vitro DC(OVA)-activated CD4+ Th cells (3 x 10(6) cells/mouse) can directly stimulate OVA-specific CD8+ T-cell responses in wild-type C57BL/6 mice and MHC II gene KO mice lacking CD4+ T cells. A large amount of CD4+ Th cells (12 x 10(6) cells/mouse) can even overcome OVA-specific immune tolerance in transgenic RIP-mOVA mice, leading to CD8+ CTL-mediated mouse pancreatic islet destruction and diabetes. The stimulatory effect of CD4+ Th cells is mediated by its IL-2 secretion and CD40L and CD80 costimulations, and is specifically delivered to OVA-specific CD8+ T cells in vivo via its acquired pMHC I complexes. Therefore, the above elucidated principles for CD4+ Th cells will have substantial implications in autoimmunity and antitumor immunity, and regulatory T-cell-dependent immune suppression. |
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Authors:
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Zhenmin Ye; Khawaja Ashfaque Ahmed; Siguo Hao; Xueshu Zhang; Yufeng Xie; Manju Ankathatti Munegowda; Qinghe Meng; Rajni Chibbar; Jim Xiang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Autoimmunity Volume: 41 ISSN: 1607-842X ISO Abbreviation: Autoimmunity Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-10-15 Completed Date: 2009-05-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8900070 Medline TA: Autoimmunity Country: England |
Other Details:
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Languages: eng Pagination: 501-11 Citation Subset: IM |
Affiliation:
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Research Unit, Departments of Oncology and Immunology, Saskatchewan Cancer Agency, College of Medicine, University of Saskatchewan, Saskatoon, Sask., Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoimmunity CD8-Positive T-Lymphocytes / immunology*, metabolism Cell Proliferation Dendritic Cells / immunology*, metabolism Diabetes Mellitus / immunology* Genes, MHC Class II Histocompatibility Antigens Class II / immunology Immune Tolerance Islets of Langerhans / cytology, immunology*, metabolism Lymphocyte Activation* Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Ovalbumin / immunology T-Lymphocytes, Helper-Inducer / immunology*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Histocompatibility Antigens Class II; 9006-59-1/Ovalbumin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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