Autoreactive T cell clones from patients with systemic lupus erythematosus support polyclonal autoantibody production.
This work examines the functional properties and TCRbeta gene utilization of 15 autoreactive T cell clones derived from five patients with systemic lupus erythematosus. All these clones proliferated and secreted cytokine when stimulated in vitro by autologous (but not allogenic) B cells. Individual T cell clones used diverse TCRbeta genes and did not show skewing toward the preferential usage of anionically charged receptors. Autoreactive T cell clones supported polyclonal B cell activation, as characterized by the production of anti-DNA, anti-Sjögren syndrome A, and anti-tetanus toxoid (anti-TT) Abs. This T cell help was mediated through the production of immunostimulatory cytokines, especially IL-6. Although stimulation of the autoreactive clones was blocked by anti-HLA class II Abs, the T cell clones did not proliferate, nor did they support polyclonal IgG production by HLA class II-matched normal B cells. Unlike the autoreactive clones, TT-specific clones derived from the same patients provided help selectively to B cells secreting anti-TT Abs. These findings suggest that autoreactive T cells from systemic lupus erythematosus patients are triggered to provide help following cognate interactions with self-peptides presented in the context of HLA class II molecules expressed on autologous B cells regardless of their specificities.
Takeno
M
M
Department of Immunology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Nagafuchi
H
H
Kaneko
S
S
Wakisaka
S
S
Oneda
K
K
Takeba
Y
Y
Yamashita
N
N
Suzuki
N
N
Kaneoka
H
H
Sakane
T
T
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015850:Interleukin-6 / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013745:Tetanus Toxoid / Q000276:immunology
D001323:Autoantibodies; D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D010455:Peptides; D013745:Tetanus Toxoid