In vitro regulation of thyroglobulin (Tg) autoantibody production by Tg-specific T-cell lines and hybridomas.
To define the interactions between self thyroglobulin (Tg)-reactive T and B we co-cultured enriched B cells taken from rat or mouse Tg-primed mice with major histocompatibility complex (MHC) class II-restricted T-cell lines specific for iodinated determinants on self-Tg, or hybridomas derived from those lines. Using two clonally distinct T-cell hybridomas, ADA2 and CH9, in vitro help for Tg autoantibody responses was observed using mouse (M)Tg-primed B cells and a 100 ng/ml MTg challenge. Using rat Tg-primed B cells and the same conditions, only CH9 provided help, indicating that the fine specificity of B cells influences their ability to interact with specific anti-Tg T-cell clones. In contrast to T-cell hybridomas, their parent T-cell lines MTg9B3 and MTg12B suppressed Tg autoantibody responses in vitro, although they augmented bystander proliferation of unprimed B cells. The MTg12B cells also (i) diminished the survival of Tg-primed B cells, and (ii) inhibited the proliferation of an antigen-presenting B-cell hybridoma (LK35.2) in a cytostasis assay. These findings together support the view that their suppressive activity is mediated through cytotoxicity. While the role of class II-restricted cytotoxic cells in thyroid autoimmunity is unknown, the results suggest that such cells may act to suppress autoantibody responses as well as to mediate tissue damage to class II-expressing thyroid cells.
Champion
B R
BR
Department of Immunology, University College and Middlesex School of Medicine, London, U.K.
Hutchings
P
P
Rayner
D C
DC
Page
K
K
Tite
J
J
Cooke
A
A
Roitt
I M
IM
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D013954:Thyroglobulin