Cellular immune mechanisms of early reproductive failure.

Approximately 15 % of couples in the United may have on reproductive events since cytokines States desiring children are unable to achieve may have both immunotrophic and immunodysa successful gestation. Pregnancy does not reach trophic effects depending on the type and concenviability in 70% of aI1 conceptions; 50% are lost tration of cytokines involved and the differentiabefore the first missed menses.’ Early reproductive tion stage of susceptible reproductive tissue failure may be attributable to failure of fertiliza- targets. In this section the immunodystrophic eftion or to failure of post-fertilization events. The fects of cytokines will be presented. A list of the occurrence of successful pregnancies in severe most completely studied human cytokines is shown combined immunodeficient mice suggests that im- in Table 3. mune mechanisms may not play a major role in The human menstrual cycle is an endocrinologipregnancy maintenance. However, immune tally mediated process for ovum maturation and mechanisms may be involved in reproductive release culminating in successful fertilization and failure. Immunologic factors have been implicated implantation. Ovarian follicular fluid contains an in up to 20% of couples with unexplained infertil- increased ratio of T-suppressor (CD8) to T-helper ity and up to 85 % of couples with unexplained re- (CD4) cells as compared with peripheral blood.5 current abortion.2,3 The reproductive events po- The finding that the ovarian follicle contains a tentially inhibited by immunologic mechanisms high proportion of CD8( +) cells suggests that acare listed in Table 1. tive immunoregulation occurs in the human ovary The female reproductive tract, like other muco- to maintain ovarian self-tolerance since adoptive sal tissues, must maintain tissue integrity while transfer experiments in rodents indicate that keeping foreign antigens (molecules capable of CD8( +) cells are required in the gonad for the eliciting an immune response) in abeyance. The prevention of autoimmunity.6s7 Cytokine homeoimmune system is a complex integrated system stasis must be maintained in the developing follicle that has evolved to protect the individual from and corpus luteum since overproduction of IFN--/ nonself tissue, yet the maternal immune system by activated T-cells can enhance major histocomdoes not normally react adversely to either pa- patibility complex (MHC) class I and induce ternal gene products or tissue-specific differentia- MHC class II transplantation antigen expression tion antigens that are unique to the maternal on granulosa cells,* resulting in loss of self-tolerhost.* Female reproductive tissues are immunolog- ance and immunologic attack culminating in ovarically dynamic, replete with antigen-presenting ian failure, or perhaps in milder cases, disordered cells and other immune cell populations capable of ovulation. IFN-7 may also interfere with ovum responding to antigenic stimulation with cytokine maturation and development by interfering with and antibody production that may either facilitate the principal cytoskeletal protein component, tuor hinder reproductive events. In this article the bulin (unpublished observation). cellular immune mechanisms implicated in early IFN--/ or TNF-cr secretion within the female rereproductive failure are reviewed (Table 2). productive tract in response to infection or seminal