Concurrent induction of antitumor immunity and autoimmune thyroiditis in CD4+ CD25+ regulatory T cell-depleted mice.

When CD4+ CD25+ regulatory T cells are depleted or inactivated for the purpose of enhancing antitumor immunity, the risk of autoimmune disease may be significantly elevated because these regulatory T cells control both antitumor immunity and autoimmunity. To evaluate the relative benefit and risk of modulating CD4+ CD25+ regulatory T cells, we established a new test system to measure simultaneously the immune reactivity to a tumor-associated antigen, neu, and an unrelated self-antigen, thyroglobulin. BALB/c mice were inoculated with TUBO cells expressing an activated rat neu and treated with anti-CD25 monoclonal antibody to deplete CD25+ cells.

Severe dilatation of saphenous vein grafts: a late complication of coronary surgery in which the diagnosis is suggested by chest x-ray.

Aneurysmal dilatation of saphenous vein graft (SVG), first reported in 1975, is secondary to true aneurysm or pseudoaneurysm. We report 1 case and review 107 cases published since 1975. Severe SVG dilatations are large (6 +/- 3 cm), occur remote from surgery (12 +/- 4 years) and are life threatening, with 15.

Pathogenic human thyroglobulin peptides in HLA-DR3 transgenic mouse model of autoimmune thyroiditis.

To identify pathogenic epitopes on human thyroglobulin (hTg), a homodimer of 660kDa, we have applied a computer-based algorithm to predict potential HLA-DR3-binding peptides and have tested them in DR3-transgenic mice. Of the 39 peptides selected, four stimulated a proliferative response from hTg-primed cells of DR3+ mice, but not DQ8+ mice. Of the four peptides, one, hTg2079, was consistently pathogenic.

Coexpression of susceptible and resistant HLA class II transgenes in murine experimental autoimmune thyroiditis: DQ8 molecules downregulate DR3-mediated thyroiditis.

Experimental autoimmune thyroiditis (EAT) can be induced in genetically susceptible mice by immunization with the self antigen, thyroglobulin (Tg). Since susceptibility is linked to H2 class II molecules, we have generated human leukocyte antigen (HLA) class II transgenic mice to study potential HLA associations with Hashimoto's thyroiditis. DR3 (HLA-DRA/DRB1*0301) and DQ8 (HLA-DQA1*0301/DQB1*0302) transgenes were introduced into class II-negative Ab(0)/B10 and Ab(0) nonobese diabetic (Ab(0)/NOD) mice.

HLA-DR and HLA-DQ polymorphism in human thyroglobulin-induced autoimmune thyroiditis: DR3 and DQ8 transgenic mice are susceptible.

In contrast to H2-based susceptibility to experimental autoimmune thyroiditis (EAT) induced with thyroglobulin (Tg), human leukocyte antigen (HLA) association with Hashimoto's thyroiditis, the human counterpart, is less clear, and determining association is further complicated by DR/DQ linkage disequilibrium. Previously, we addressed the controversial implication of HLA-DR genes by introducing HLA-DRA/DRB1*0301 (DR3) transgene into endogenous class II negative H2Ab(0) mice. EAT induction with either human (h) or mouse (m) Tg demonstrated the permissiveness of DR3 molecules for shared Tg epitopes.