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Peptide‐activated double‐negative T cells can prevent autoimmune type‐1 diabetes development
Author(s) -
Ford Megan S.,
Chen Wenhao,
Wong Sophie,
Li Carmen,
Vanama Ramesh,
Elford Alisha R.,
Asa Sylvia L.,
Ohashi Pamela S.,
Zhang Li
Publication year - 2007
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200636991
Subject(s) - biology , cd8 , t cell , t cell receptor , cytotoxic t cell , antigen , antigen presenting cell , microbiology and biotechnology , immunology , major histocompatibility complex , in vitro , immune system , biochemistry
Abstract Autoimmune diseases may develop because of defective maturation, activation, differentiation and function of regulatory T cells. Previous studies have shown that exposure to donor antigen activates peripheral TCRαβ + CD3 + CD4 – CD8 – NK1.1 – , double‐negative (DN) T cells, which specifically suppress anti‐donor T cells and enhance survival of skin and heart grafts from allogeneic and xenogeneic donors. However, the role of DN T cells in preventing T cell‐mediated autoimmune disease is unknown. Here, we analyzed the ability of DN T cells to recognize peptides expressed on self MHC and to suppress peptide‐reactive CD8 + T cells, using the P14 mouse model that expresses a transgenic TCR specific for gp33 peptide presented on self MHC class I‐D b . We found that injection of gp33 peptide resulted in increased DN and decreased CD8 + T cell numbers in the lymph nodes when compared to untreated mice. Injection of gp33, but not TCR‐non‐specific AV peptide, increased expression of T cell activation markers on DN T cells. Moreover, gp33‐activated DN T cells suppressed proliferation of syngeneic CD8 + T cells via killing activated CD8 + T cells in an antigen‐specific fashion in vitro . Furthermore, transferring gp33‐activated DN T cells inhibited the development of autoimmune diabetes, suggesting that DN T cells may provide a novel therapy for T cell‐mediated autoimmune diseases.