Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer.

Abstract

Neonatal thymectomy during the critical period, 2-4 d after birth, can induce various organ-specific autoimmune diseases including oophoritis in A/J mice. The oophoritis thus induced was passively transferred into neonatal mice by injection of spleen cells obtained from syngeneic donors with the disease. Recipient ovaries were rapidly damaged with remarkable mononuclear cell infiltration and destruction of follicular structures. The phenotype of effector cells responsible for successful adoptive transfer was found to be Thy-1+, Lyt-1+,23-, Ia-, Qa-1-, and was sensitive to antithymocyte serum treatment but resistant to cyclophosphamide treatment or in vitro X-ray irradiation. The compatibility between donor and recipient at the major histocompatibility complex was not required for the effector phase of transfer. The oophoritis induced in BALB/c (nu/+ or +/+) was also shown to be transferred into athymic BALB/c nude mice with resulting ovarian lesion and circulating autoantibodies against oocytes. In this transfer system, the effector cells were also demonstrated to be T cells with the Lyt-1+,23- phenotype. Adoptive transfer experiments in both systems revealed that the destruction of ovaries in postthymectomy autoimmune oophoritis was mediated by Lyt-1 T cells. Whether these T cells can be distinguished from other Lyt-1 cells, such as T helper cells and effector T cells in delayed-type hypersensitivity (DTH), is not clear at present, but the results suggest that the effector mechanisms may be closely related to a DTH reaction.

Regulatory T cells – a brief history and perspective

“…CD4 + T cells and CD4 + CD8 -mature thymocytes in particular inhibited NTx-induced murine autoimmune disease [17]. On the other hand, once autoimmunity developed, CD4 + T cells were able to adoptively transfer disease to syngeneic T cell-deficient mice as helper T cells for autoantibody formation and effectors of cell-mediated immune destruction [19].…”

Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation.

“…Tx was performed on day 3 after birth (the day of birth as day 0). Mice were anesthesized by keeping them in crushed ice for 2-3 min, and the thymus was removed en bloc under a dissecting microscope with a cottonhead toothpick (25). Sham Tx was performed by cutting the sternum without removal of the thymus.…”

Premature Ovarian Failure and Ovarian Autoimmunity

“…That animal oö phoritis is directly due to autoimmune T cells is shown by transfer experiments of CD4 ϩ T cells of thymectomized donors to young recipients, which causes an oö phoritis in these recipients (282,283). This transfer of oö-phoritis could be prevented by infusion of CD4 ϩ CD5 ϩ T cells from normal adult mice in an early stage after the transfer of the CD4 ϩ cells of the thymectomized donors.…”