PARENT SESSION
Reproductive Immunology
428
SUSCEPTIBILITY OF FRESHLY ISOLATED OVINE TROPHOBLAST CELLS AND A TROPHOBLAST DERIVED CELL LINE TO LYSIS BY CYTOTOXIC PERIPHERAL BLOOD LYMPHOCYTES.
Tekin, Saban 1, Hansen, Peter1, 1
ABSTRACT- In several species, trophoblast is resistant to cytotoxic lymphocytes (CTL). Such resistance is believed to contribute to survival of the semiallogenic conceptus. Here, it was tested whether ovine trophoblast cells are susceptible to lysis by CTL in peripheral blood; whether, if present, CTL are restricted in their specificity and activated by interleukin-2 (IL-2); and whether trophoblast cells are made more susceptible to lysis by infection with bovine herpes virus-1 (BHV-1). Placentae were collected from pregnant ewes at d 51-91 of gestation (n=6). Fresh trophoblast cells were prepared from the chorion, labeled with 51Cr, and incubated for 20 h at 50:1 and 100:1 ratios with peripheral blood lymphocytes (PBL) from the pregnant mother or from a third-party ewe. In the absence of IL-2, there was no killing of trophoblast by 3rd-party PBL, regardless of whether PBL were from pregnant or nonpregnant donors. Moreover, trophoblast was resistant to CTL from 3rd-party PBL even after infection with BHV-1. In contrast, trophoblast cells from 2 of 4 placentae tested were lysed by maternal PBL (donor × PBL type, P<0.0001). For example, the % killing at a 50:1 ratio was 0% for all trophoblast incubated with 3rd-party PBL vs 42.0%, 13.1%, 0% and 0% for trophoblast incubated with maternal PBL. Incubation with IL-2 induced CTL in 3rd-party PBL for 1 of 6 trophoblast preparations only. For the two placentae in which maternal PBL did not lyse trophoblast, addition of IL-2 did not lead to activation of CTL. A cell line derived from a CTL-resistant trophoblast became susceptible to killing by 3rd-party PBL, indicating de-differentiation of the molecular mechanisms allowing the trophoblast to evade maternal CTL. It is suggested that the killing of ovine trophoblast by specific maternal CTL or, less frequently, nonspecifically by lymphokine activated killer cells can occur and may contribute to pregnancy loss. (Support: USDA NRICGP 96-35203).
KEY WORDS: Trophoblast, IL-2, BHV-1, Ovine