FAS/FAS ligand interaction at the placental interface is not required for the success of allogeneic pregnancy in anti-paternal MHC preimmunized mice.
OBJECTIVE
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?


METHODS
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/B1/6.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 C57B1/6 to enhance the likelihood of fetal rejection and/or runting. Cytotoxic lymphocyte (CTL) activity in the spleens was assessed using a 51Cr-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.
Chaouat
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G
Equipe cytokines dans la relation materno foetale, Maternité: H pital Antoine Béclère, Clamart, France. chaouatg@worldnet.fr
Clark
D A
DA
D000818:Animals; D053222:Fas Ligand Protein; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007114:Immunization; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D019014:fas Receptor