Document Detail


Th1 cell anergy and blockade in G1a phase of the cell cycle.
MedLine Citation:
PMID:  8335926     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human gamma-globulin (HGG)-specific Th1 cells exposed to HGG presented by chemically fixed spleen cells are blocked in G1a phase when challenged subsequently with HGG. The present study made use of the G1a blocker n-butyrate to further examine the relationship between tolerance induction and cell cycle progression. Th1 cells from primary cultures containing n-butyrate together with HGG and immunogenic, nonfixed APC lost their ability to proliferate or secrete IL-2 in HGG-stimulated secondary cultures. In contrast to their lack of responsiveness to secondary Ag challenge, Th1 cells exposed to n-butyrate and HGG proliferated normally in secondary cultures stimulated with IL-2. The suppressive effects of n-butyrate appear to require TCR occupation; Th1 cells exposed to n-butyrate in the absence of HGG did not lose their ability to proliferate in Ag-stimulated secondary cultures. In addition, although both HGG-presenting APC and IL-2 stimulate Th1 cell cycle progression into G1a, only HGG-presenting APC induced Th1 cell anergy in conjunction with n-butyrate. Unlike n-butyrate, drugs that blocked Th1 cell cycle progression in G0, G1b, or S/G2 phases did not inhibit subsequent Ag-specific proliferation by Th1 cells. Thus it appears that n-butyrate-induced G1a sequestration, in association with TCR occupancy, induces Th1 cell anergy.
Authors:
K M Gilbert; W O Weigle
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  151     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1993 Aug 
Date Detail:
Created Date:  1993-08-26     Completed Date:  1993-08-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1245-54     Citation Subset:  AIM; IM    
Affiliation:
Scripps Research Institute, Department of Immunology, La Jolla, CA 92037.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen-Presenting Cells / immunology
Antigens / immunology*
Butyrates / pharmacology
Cell Cycle* / drug effects
Immune Tolerance*
Interleukin-2 / biosynthesis
Lymphocyte Activation / drug effects
Male
Mice
Mice, Inbred A
T-Lymphocyte Subsets / cytology,  immunology*
T-Lymphocytes, Helper-Inducer / cytology*,  immunology*
Grant Support
ID/Acronym/Agency:
AG01743/AG/NIA NIH HHS; AI15761/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens; 0/Butyrates; 0/Interleukin-2

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