The effect of adding a surfeit of autologous CD8+ T cells to SCID mice after secondary rexenografts of Graves' thyroid tissue.
To investigate the effect of adding a surfeit of CD8+ T cells as a potential immunoregulator in Graves' disease (GD), thyroid tissues from 4 patients with GD and 2 normal subjects (N) were initially xenografted into nude mice. Eight weeks after xenografting, the thyroid tissues, which were then devoid of lymphocytes and appeared normal, were retrieved from the nude mouse, and rexenografted (rexenografts) into severe combined immuno-deficient (SCID) mice; 20 x 10(6) of autologous peripheral blood mononuclear cells (PMBC) or 20 x 10(6) of CD8(+)-depleted PBMC ("non-CD8 cells," i.e., CD4-enriched PBMC) were simultaneously engrafted into SCID mice with thyroid rexenografts. In addition, 20 x 10(6) of CD8(+)-enriched PBMC ("CD8-doubled" cells, which were prepared to double the percentage of CD8+ T cells compared to that of PBMC) were engrafted into SCID mice with rexenografts from 2 GD and 2 N; finally, 20 x 10(6) of PBMC plus an extra 10 x 10(6) of CD8+ T cells ("extra-CD8 added" cells, total 30 x 10(6) of CD8-enriched cells) were engrafted into separate SCID mice with rexenografts from 2 GD. The reengraftment of GD rexenografts or N rexenografts alone did not result in the detection of thyroperoxidase (TPO)-antibodies (Abs), thyroglobulin (Tg)-Abs, thyroid-stimulating Ab (TSAb) production, human IgG, or lymphocytic infiltration in the xenografts. However, the engraftment of either autologous PBMC or non-CD8 cells from patients with GD and N into SCID mice with rexenografts caused human IgG to become detectable and then rise further in 10 of 17 SCID mice; when human IgG, TPO-Ab, Tg-Ab, and TSAb were quantitated, GD rexenografts plus non-CD8 cells engrafted into SCID mice showed a higher production of each antibody and human IgG than in GD rexenografts plus PBMC, or GD rexenografts plus CD8-doubled cells, or GD rexenografts plus extra "CD8-added" cells. Moreover, when CD8-doubled cells or extra CD8-added cells with rexenografts were engrafted to SCID mice with rexenografts, they showed generally lower production of human IgG and thyroid antibodies compared to SCID mice into which PBMC were engrafted with rexenografts, despite the fact that 50% more cells (30 x 10(6)) were engrafted in the preparations of extra CD8-added cells. In conclusion, CD8+ T cells from patients with GD appeared to suppress the induction of thyroid antibodies, TSAb, and human IgG. The CD8+ cells thus are acting as suppressor or regulatory T cells. Such cells might be important in the pathogenesis of autoimmune thyroid disease.
Mukuta
T
T
Endocrinology Research Laboratory, Wellesley Hospital, University of Toronto, Ontario, Canada.
Nishikawa
M
M
Arreaza
G
G
Resetkova
E
E
Yoshikawa
N
N
Fornasier
V
V
Young
E
E
Volpé
R
R
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D006111:Graves Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007700:Kinetics; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D013961:Thyroid Gland / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous
D001323:Autoantibodies; D006684:HLA-DR Antigens; D007074:Immunoglobulin G