Document Detail


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.
MedLine Citation:
PMID:  18855194     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Autoimmunity     Volume:  41     ISSN:  1607-842X     ISO Abbreviation:  Autoimmunity     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-15     Completed Date:  2009-05-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8900070     Medline TA:  Autoimmunity     Country:  England    
Other Details:
Languages:  eng     Pagination:  501-11     Citation Subset:  IM    
Affiliation:
Research Unit, Departments of Oncology and Immunology, Saskatchewan Cancer Agency, College of Medicine, University of Saskatchewan, Saskatoon, Sask., Canada.
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MeSH Terms
Descriptor/Qualifier:
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:
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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