Regulatory Function of in vivo Anergized CD4+T Cells

It has been suggested that anergic T cells may not be only inert cells but may rather play an active role, for example by regulating immune responses. We have previously reported the existence of "anergic" IL-10-producing CD4+T cells generated in vivo by continuous antigenic stimulation. U...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-07, Vol.98 (15), p.8738-8743
Main Authors: Jooss, K, Gjata, B, Danos, O, von Boehmer, H, Sarukhan, A
Format: Article
Language:English
Subjects:
Adenoviruses, Human
Animals
Antigens
Biological Sciences
CD4-Positive T-Lymphocytes - immunology
Cells
Clonal Anergy - immunology
Dependovirus
Gene Expression
Genes
Genetic Vectors
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Humans
Immune response
Immune Tolerance - immunology
Immunology
Mice
Mice, Inbred BALB C
Mice, Transgenic
Muscle fibers
Proteins
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - immunology
T cell antigen receptors
T lymphocytes
Transgenic animals
Transplantation tolerance
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Summary:It has been suggested that anergic T cells may not be only inert cells but may rather play an active role, for example by regulating immune responses. We have previously reported the existence of "anergic" IL-10-producing CD4+T cells generated in vivo by continuous antigenic stimulation. Using a gene transfer system where the antigen recognized by such T cells is expressed in skeletal muscle by two different DNA viral vectors, we show that these cells not only remain tolerant toward their cognate antigen but also can suppress the immune response of naïve T cells against the immunogenic adenoviral proteins. Furthermore, they can completely inhibit tissue destruction that takes place as a result of an immune response. The system presented here is unique in that the T cells have been anergized in vivo, their antigen specificity and functional status are known, and the amount, form, and timing of antigen expression can be manipulated. This model will therefore permit us to carefully dissect the mechanisms by which these anergic T cells regulate the priming and/or effector function of naïve T cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.151088898