Anamnestic development of lymphocytic infiltration in murine experimental autoimmune oophoritis is primarily localized in the stroma and theca.
OBJECTIVE
Neonatal thymectomy performed on day 3 of life (NTX3) induces autoimmune oophoritis and ovarian failure in B6A mice. These mice develop high-titer autoantibodies specific to oocytes, and ultimately the ovaries become fibrotic and devoid of primordial follicles. These findings implicate the oocyte as a primary target of the autoimmune process. However, in previous work we demonstrated that in developing disease the lymphocytic infiltration was confined to the stroma and theca, and not found involving oocytes. Here, we investigate the possibility that lymphocytic infiltration involving oocytes develops as part of end-stage disease.


METHODS
We transplanted normal syngeneic ovaries to B6A mice with confirmed autoimmune ovarian failure, and, as a control, to normal oophorectomized mice. We then defined the time course and histologic distribution of lymphocytic infiltration in the transplanted ovaries. Lymphocytes were identified by morphology with the aid of an immunohistochemical leukocyte marker (CD45).


RESULTS
Autoimmune oophoritis developed by 7 days after transplantation to the NTX3 mice. Compared to control mice, in these mice we found significantly increased stromal and thecal lymphocytic infiltration. In no case did we observe lymphocytic infiltration involving oocytes.


CONCLUSIONS
Our findings agree with our previous report and suggest that the ovarian failure in this model is not mediated by a direct lymphocytic attack against intact oocytes. Other immune-mediated mechanisms are responsible. The paradoxical development of high-titer oocyte-specific antibodies despite the stromal and thecal location of the lymphocytic infiltration remains to be explained.
Raj
S
S
Department of Obstetrics and Gynecology, Louisiana State University Medical Center, New Orleans, USA.
Nair
S
S
Mastorakos
G
G
Nelson
L M
LM
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009869:Oophoritis / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D017154:Stromal Cells / Q000276:immunology* / Q000473:pathology; D013799:Theca Cells / Q000276:immunology* / Q000473:pathology