THE EFFECT OF ADDING A SURFEIT OF AUTOLOGOUS CD8-CELLS TO SCID MICE AFTER SECONDARY REXENOGRAFTS OF GRAVES THYROID-TISSUE( T)

To investigate the effect of adding a surfeit of CD8(+) T cells as a p otential immunoregulator in Graves' disease (GD), thyroid tissues from 4 patients with GD and 2 normal subjects (N) were initially xenograft ed into nude mice. Eight weeks after xenografting, the thyroid tissues , which were then devoid of lymphocytes and appeared normal, were retr ieved from the nude mouse, and rexenografted (rexenografts) into sever e combined immunodeficient (SCID) mice; 20x10(6) of autologous periphe ral blood mononuclear cells (PMBC) or 20x10(6) of CD8(+)-depleted PBMC (''non-CD8 cells,'' i.e., CD4-enriched PBMC) were simultaneously engr afted into SCID mice with thyroid rexenografts. In addition, 20x10(6) of CD8(+)-enriched PBMC (''CD8-doubled'' cells, which were prepared to double the percentage of CD8(+) T cells compared to that of PBMC) wer e engrafted into SCID mice with rexenografts from 2 GD and 2 N; finall y, 20x10(6) of PBMC plus an extra 10x10(6) of CD8(+) T cells (''extra- CD8 added'' cells, total 30x10(6) of CD8-enriched cells) were engrafte d into separate SCID mice with rexenografts from 2 GD. The reengraftme nt of GD rexenografts or N rexenografts alone did not result in the de tection of thyroperoxidase (TPO)-antibodies (Abs), thyroglobulin (Tg)- Abs, thyroid-stimulating Ab (TSAb) production, human IgG, or lymphocyt ic 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, an d TSAb were quantitated, GD rexenografts plus non-CD8 cells engrafted into SCID mice showed a higher production of each antibody and human I gG than in GD rexenografts plus PBMC, or GD rexenografts plus CD8-doub led cells, or GD rexenografts plus extra ''CD8-added'' cells. Moreover , when CD8-doubled cells or extra CD8-added cells with rexenografts we re engrafted to SCID mice with rexenografts, they showed generally low er production of human IgG and thyroid antibodies compared to SCID mic e into which PBMC were engrafted with rexenografts, despite the fact t hat 50% more cells (30x10(6)) were engrafted in the preparations of ex tra 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 regulato ry T cells. Such cells might be important in the pathogenesis of autoi mmune thyroid disease.