Increased severity of spontaneous autoimmune thyroiditis (SAT) and salivary gland infiltration in NOD.H-2h4 mice lacking regulatory T cells (T reg) (143.25)

Abstract

Abstract NOD.H-2h4 mice given NaI in the drinking water develop SAT with chronic inflammation of the thyroid by T and B cells and production of anti-thyroglobulin (Tg) autoantibody. CD28-/- NOD.H2-4 mice, which have greatly reduced numbers of CD4+CD25+FoxP3+ Treg, were developed in order to examine the role of T reg in SAT development in WT and B cell-deficient (B-/-) mice. CD28-/- NOD.H2-h4 mice given NaI water develop more severe SAT than WT mice with collagen deposition (fibrosis) and low serum T4. Lymphocyte infiltration of salivary glands is also increased compared to WT mice. Most 4-6 mo old CD28-/- mice not given NaI water also develop SAT, whereas WT NOD.H-2h4 mice not given NaI water rarely develop SAT until much later. Although anti-Tg autoantibody levels generally correlate with SAT severity in WT mice, CD28-/- mice have reduced anti-Tg autoantibodies. Over time, the percentage of splenic follicular B cells decreases and marginal zone B cells increase. B -/- NOD.H-2h4 mice are resistant to SAT, but they develop SAT after transient depletion of T reg. CD28-/-B-/- mice, which lack most T reg, develop SAT comparable to WT NOD.H-2h4 mice. In B-/- mice, a lack of B cells as APC during the initiation phase of SAT may lead to preferential activation of Treg leading to reduced activation of effector T cells and reduced SAT severity. T reg also regulate SAT development if B cells are present since severe SAT develops in CD28-/- mice lacking T reg. (Supported by NIH RO1 AI076395)