INHIBITION OF IMMUNOPROTECTIVE CD8(-CELLS AS A BASIS FOR STRESS-TRIGGERED SUBSTANCE P-MEDIATED ABORTION IN MICE() T)

The embryo expresses paternal antigens foreign to the mother and there fore has been viewed as an allograft. The maternal immune system respo nds to paternal antigens on the ''graft,'' and these responses are tho ught 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 neurotransmit ter substance P-dependent pathway. Immunization protects against stres s-triggered abortion and CD8(+) T cells appear to be required. The obj ective of the present study was to investigate the importance of CD8() T cells in the prevention of stress-triggered abortion by immunizati on. Injection of anti-CDS increased the abortion rate in nonimmunized mice and in immunized mice. Following anti-CD8 injection, stress faile d to further increase the abortion rate; a similar high rate of aborti on was seen in immunized and anti-CD8-injected mice. These data sugges ted that stress could act by neutralization and/or elimination of immu noprotective CD8(+) T cell function. CD8(+) T cells from pregnant mice have been reported to produce a 34-kDa suppresser factor, but we dete cted a 1.5- to 2-kDa suppressive factor in the HPLC fractions of super natants obtained from nonstressed decidua, and this activity was aboli shed by stress and boosted by immunization with Balb/c cells. (C) 1996 Academic Press, Inc.