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.
Shiraishi
H
H
Department of Obstetrics and Gynecology, School of Medicine, Nihon University, Tokyo, Japan.
Hayakawa
S
S
Satoh
K
K
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