Regulation of the induction and resolution of granulomatous experimental autoimmune thyroiditis in mice by CD8+ T cells.
Mouse thyroglobulin (MTg)--sensitized spleen cells activated in vitro with MTg induce experimental autoimmune thyroiditis (EAT) in which the thyroid cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Cells cultured with MTg plus anti-IL2R antibody induce EAT having a granulomatous histopathology. CD4+ T cells are required to induce both forms of EAT. The potential contribution of CD8+ T cells in the pathology of lymphocytic vs granulomatous EAT was addressed using anti-CD8 mAb to deplete CD8+ T cells from donor or recipient mice. Depletion of donor CD8+ T cells had little effect on EAT severity induced by cells cultured with MTg or MTg plus anti-IL2R mAb. However, recipients of CD8-depleted cells activated with MTg induced granulomatous EAT whereas cells from untreated donors activated with MTg alone induced lymphocytic EAT. Similar results were obtained when anti-CD8 mAb was added to cultures to block activation of CD8+ T cells. Injection of anti-CD8 mAb into recipient mice slightly increased the severity of EAT induced by cells cultured with MTg or MTg and anti-IL2R mAb when EAT was assessed 19-20 days after cell transfer. Cells cultured with MTg alone induced mild granulomatous EAT in most anti-CD8-treated recipients. When thyroids of mice which had granulomatous EAT on Day 19 were examined 47 or 60 days after cell transfer, the granulomatous inflammatory response in untreated recipients had almost completely resolved. In contrast, granulomatous EAT persisted and often became more severe in anti-CD8-treated recipients. Anti-CD8 treatment did not influence lymphocytic EAT assessed late after cell transfer. These results indicate that CD8+ T cells are required for the resolution of granulomatous EAT.
Braley-Mullen
H
H
Department of Medicine, University of Missouri, Columbia 65212.
McMurray
R W
RW
Sharp
G C
GC
Kyriakos
M
M
D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology; D016827:CD8 Antigens; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000276:immunology; D007116:Immunization, Passive; D008212:Lymphocyte Depletion; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology*
D000961:Antilymphocyte Serum; D016827:CD8 Antigens; D013954:Thyroglobulin