Inhibition of immunoprotective CD8+ T cells as a basis for stress-triggered substance P-mediated abortion in mice.

The embryo expresses paternal antigens foreign to the mother and therefore has been viewed as an allograft. The maternal immune system responds to paternal antigens on the "graft", and these responses are thought to protect pregnancy. However, pregnancy can be aborted by stress, which stimulates local production of TNF-alpha and inhibits TGF-beta 2-producing natural suppressor cell (NS) activity via a neurotransmitter substance P-dependent pathway. Immunization protects against stress-triggered abortion and CD8+ T cells appear to be required. The objective of the present study was to investigate the importance of CD8+ T cells in the prevention of stress-triggered abortion by immunization. Injection of anti-CD8 increased the abortion rate in nonimmunized mice and in immunized mice. Following anti-CD8 injection, stress failed to further increase the abortion rate; a similar high rate of abortion was seen in immunized and anti-CD8-injected mice. These data suggested that stress could act by neutralization and/or elimination of immunoprotective CD8+ T cell function. CD8+ T cells from pregnant mice have been reported to produce a 34-kDa suppressor factor, but we detected a 1.5- to 2-kDa suppressive factor in the HPLC fractions of supernatants obtained from nonstressed decidua, and this activity was abolished by stress and boosted by immunization with Balb/c cells.