B7.2 has opposing roles during the activation versus effector stages of experimental autoimmune thyroiditis.
APCs provide costimulatory and down-regulatory signals to Ag-activated T cells through interactions between B7.1 and B7.2 on APCs with either CD28 or CTL Ag-4 expressed on T cells. Recipients of mouse thyroglobulin (MTg)-primed spleen cells activated in the presence of anti-B7.2 had decreased experimental autoimmune thyroiditis (EAT) severity compared with recipients of cells cultured with control rat Ig or anti-B7.1. Blocking B7.2 during in vivo priming also suppressed the ability of MTg-primed spleen cells to transfer EAT, implicating a role for B7.2 for priming and in vitro activation of EAT effector cells. In contrast, administration of anti-B7.2 or anti-B7.2 Fab to recipients of MTg-activated spleen cells increased the severity of EAT compared with recipients receiving control Ig. Thyroids from anti-B7.2-treated recipients had increased expression of IL-4 mRNA compared with thyroids from rat Ig-treated controls. Both B7.1 and B7.2 molecules were expressed in the thyroids of mice with EAT, although B7.2 was more prevalent than B7.1. Administration of both anti-B7.1 and anti-B7.2 to recipient mice suppressed the development of EAT, while anti-B7.1 treatment alone had no effect on EAT severity. The suppression of EAT was not observed when anti-B7.1 and anti-B7.2 treatment was delayed until 7 days after cell transfer, suggesting a requirement for B7 in the initiation of EAT in recipient mice. These results suggest that costimulation is required during the effector phase of EAT and that B7.2 may have opposing roles in the activation versus effector stages of autoreactive T cells.
Peterson
K E
KE
Departments of Molecular Microbiology and Immunology, Pathology, and Internal Medicine, University of Missouri, Columbia, MO 65212, USA.
Sharp
G C
GC
Tang
H
H
Braley-Mullen
H
H
D000069594:Abatacept; D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D001483:Base Sequence; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018796:Immunoconjugates; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control