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Departments of
*
Pathology and
Microbiology, University of Virginia, Charlottesville, VA 22908
Female (C57BL/6xA/J)F1 mice undergoing thymectomy on
day 3 after birth (d3tx) developed autoimmune ovarian disease
(AOD) and autoimmune disease of the lacrimal gland. As both were
prevented by normal adult CD25+ T cells, regulatory T cell
depletion is responsible for d3tx diseases. AOD began as oophoritis at
3 wk. By 4 wk, AOD progressed to ovarian atrophy with autoantibody
response against multiple oocyte Ag of early ontogeny. The requirement
for immunogenic endogenous ovarian Ag was investigated in d3tx female
mice, d3tx male mice, and d3tx neonatally ovariectomized (OX) females.
At 8 wk, all mice had comparable lacrimalitis but only those with
endogenous ovaries developed AOD in ovarian grafts. The duration of Ag
exposure required to initiate AOD was evaluated in d3tx mice OX at 2,
3, or 4 wk and engrafted with an ovary at 4, 5, or 6 wk,
respectively. The mice OX at 2 wk did not have oophoritis whereas
80% of mice OX at 3 or 4 wk had maximal AOD, thus Ag stimulus for
2.5 wk following d3tx is sufficient. AOD progression requires
additional endogenous Ag stimulation from the ovarian graft. In mice OX
at 3 wk, ovaries engrafted at 5 wk had more severe oophoritis than
ovaries engrafted at 6 or 12 wk; moreover, only mice engrafted at 5 wk
developed ovarian atrophy and oocyte autoantibodies. Similar results
were obtained in mice OX at 4 wk. Thus endogenous tissue Ag are
critical in autoimmune disease induction and progression that occur
spontaneously upon regulatory T cell depletion.
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