Inhibition of lymphocyte proliferation and activation: a mechanism used by equine invasive trophoblast to escape the maternal immune response.

At days 36-38 of gestation, the equine invasive trophoblast cells migrate into the endometrium of the pregnant mare to form the endometrial cups. During their migration, they become surrounded by maternal CD4+ and CD8+ T lymphocytes, and stimulate a cytotoxic antibody response to the paternal major histocompatibility complex class I antigens that they express. Nevertheless, endometrial cup cells remain viable at the site of uterine invasion up to days 80-100 of gestation, suggesting the participation of immunomodulatory mechanisms to the maternal cellular immune response. To determine the effects of the invasive trophoblast cells on lymphocyte proliferation, an in vitro co-culture system was developed using isolated equine invasive trophoblast cells and peripheral blood lymphocytes. Fetal fibroblast cells from the same conceptuses were used as controls. The presence of invasive trophoblast cells or their pre-conditioned medium inhibited 50% or more of lymphocyte proliferation, while fetal fibroblasts had no effect. The invasive trophoblast cell inhibitory factor needed to be present constantly to affect lymphocyte proliferation, and it was ineffective if lymphocytes had been previously stimulated to proliferate. The lymphoproliferative inhibitory mechanism affected lymphocyte subpopulations similarly. In addition, lymphocyte expression of cytokine mRNA including IFNgamma, IL-2, IL-4, and IL-10 was affected compared to controls. The implication of these observations in vivo may explain, in part, the apparent equine maternal immune acceptance of the presence and development of endometrial cup cells. (c) Elsevier Ltd. All rights reserved.