FAS/FAS Ligand Interaction at the Placental Interface is not Required for the Success of Allogeneic Pregnancy in Anti‐Paternal MHC Preimmunized Mice
Journal Articles
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
PROBLEM: FAS ligand (FASL) induces apoptosis in FAS+ T cells. FAS–FASL interaction can explain tolerance of some types of allografts. Do similar interactions prevent rejection of the fetal allograft and transplacental passage of maternal T cells capable of causing GvH leading to runting? METHOD OF STUDY: We examined growth of subcutaneous EL‐4 (H‐2b) tumor cells in syngeneic MRL.lpr/lpr mice mated with syngeneic MRL.lpr/lpr or allogeneic C57/Bl/6.lpr/lpr males. Lpr/lpr mice lack FAS and their T cells should remain effective at the fetomaternal interface. In some studies, the mice were preimmunized against C57Bl/6 to enhance the likelihood of fetal rejection and/or runting. Cytotoxic lymphocyte (CTL) activity in the spleens was assessed using a image
Cr‐release assay. Birth weights and weights at weaning were measured.
RESULTS: Tumor rejection was delayed by about 3 days in allopregnant lpr/lpr females compared to syngeneic pregnant females occurred, but tumors were rejected and in a secondary fashion with minimal delay allopregnant females preimmunized to H‐2b. CTL activity was present more in decidua than in spleen in preimmunized mice, and allopregnancy failed to reduce this activity. No neonates born to preimmunized or control lpr/lpr mothers developed runt disease. Indeed, the birth weight was greater for immunized females, but at 10 weeks, the difference compared to non‐immunized females disappeared.
CONCLUSIONS: FAS/FASL interaction between FAS+ T cells and FASL+ fetal trophoblasts at the fetomaternal interface is not mandatory for successful allopregnancy. The potential roles of other apoptosis‐induction mechanisms at the fetomaternal interface, such as TNF/TRAIL, require critical testing before enthusiasm is merited. It maybe necessary to eliminate all such mechanisms to show a deleterious effect on pregnancy. Spontaneous deletion of all pathways seems a priori unlikely to occur, and hence, of dubious relevance to fetal loss.
