Document Detail


B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors.
MedLine Citation:
PMID:  9036945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The B7 family of costimulatory molecules provides the second signal necessary for activation of T cells. In the absence of the second signal, responding T cells become anergic. Although predominantly expressed on professional APCs, recent evidence shows that the B7 molecules are also expressed on T cells. To study the functions of B7 molecules on T cells, we transfected murine B7.1 (CD80) and B7.2 (CD86) cDNAs into the EL4 T cell thymoma cell line and examined the transfectants for their ability to costimulate T cell proliferation in vitro and to induce antitumor immunity in vivo. Here we show that although EL4-B7.1 cells costimulate T cells and induce tumor regression, EL4-B7.2 transfectants failed to costimulate T cell proliferation or induce tumor regression. To understand the cellular basis for this difference, we examined the binding of EL4-B7.1 and EL4-B7.2 to CTLA4 and CD28. Whereas EL4-B7.1 cells bound both CTLA4-Ig and CD28-Ig, EL4-B7.2 transfectants preferentially bound CTLA4-Ig, but not CD28-Ig. Similar binding data were obtained with freshly isolated murine T cells, which have been shown to constitutively express B7.2. Our data suggest, therefore, that B7.2 expressed on T cells may not costimulate but instead inhibit the T cell response by preferential binding to CTLA4.
Authors:
E A Greenfield; E Howard; T Paradis; K Nguyen; F Benazzo; P McLean; P Höllsberg; G Davis; D A Hafler; A H Sharpe; G J Freeman; V K Kuchroo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  158     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-03-11     Completed Date:  1997-03-11     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2025-34     Citation Subset:  AIM; IM    
Affiliation:
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / biosynthesis*,  metabolism,  pharmacology*
Antigens, CD28 / metabolism,  physiology*
Antigens, CD86
Antigens, Differentiation / metabolism*
CTLA-4 Antigen
Cell Division
Female
Immunoconjugates*
Lymphocyte Activation*
Membrane Glycoproteins / biosynthesis*,  metabolism,  pharmacology*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Protein Binding / immunology
T-Lymphocytes / immunology,  metabolism*
Thymoma / immunology*,  prevention & control
Thymus Neoplasms / immunology*,  prevention & control
Transfection / immunology
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
NS 30843/NS/NINDS NIH HHS; P01 AR43220/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD28; 0/Antigens, CD86; 0/Antigens, Differentiation; 0/CTLA-4 Antigen; 0/Cd86 protein, mouse; 0/Ctla4 protein, mouse; 0/Immunoconjugates; 0/Membrane Glycoproteins; 7D0YB67S97/abatacept

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