Murine experimental abortion by IL-2 administration is caused by activation of cytotoxic T lymphocytes and placental apoptosis.
OBJECTIVE
Fetal loss caused by IL-2 administration to pregnant mice is regarded as a model of human habitual abortion due to allo-immune reactions. To estimate feto-placental damages in this model, we examined apoptosis histochemically in the placenta.


METHODS
Four allogenic mated mice were administered intraperitoneally with 1000 IU of recombinant human IL-2 on days 3, 5 (7) after mating. We examined the presence of apoptosis in the placentae by TUNEL stain. We also examined expression of CTL specific granzyme B/perforin mRNA and usage of TCR V beta receptor segments by RT-PCR.


RESULTS
1. Allogenic pregnant mice given IL-2 revealed increased apoptotic scores in villous trophoblasts compared with control mice. Extracted DNA from IL-2 treated placentae revealed ladder formations. 2. Expression of granzyme B mRNA was increased while expression of perforin mRNA was not changed. 3. We observed increased numbers of TCR V beta gene segments in the decidua from IL-2 treated mice compared with untreated mice.


CONCLUSIONS
We suggest that placental apoptosis caused by activation of maternal CTL may play important roles in the rejection of fetal allografts.
Department of Obstetrics and Gynecology, School of Medicine, Nihon University, Tokyo, Japan.
H
H
Shiraishi
S
S
Hayakawa
K
K
Satoh
D000028:Abortion, Induced; D000818:Animals; D017209:Apoptosis; D005260:Female; D053804:Granzymes; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*
D007376:Interleukin-2; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases