The Journal of Immunology, Vol 152, Issue 10 4903-4911, Copyright © 1994 by American Association of Immunologists

ARTICLES

Maternal anti-placental reactivity in natural, immunologically-mediated fetal resorptions

S Tangri, TG Wegmann, H Lin and R Raghupathy
Immunogenetics Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.

Observations on maternal recognition of the fetus and the demonstration of the effects of cytokines on reproductive events led to the "immunotrophism" model, which suggests that maternal immune recognition of fetally-derived Ags results in the release of cytokines that promote the growth of the placenta; any disturbance in this balance of cytokines could result in deleterious consequences for the placenta and, in turn, the fetus. We have focused our attention on the murine CBA/J x DBA/2 model of spontaneous abortions and compared them with normal CBA x BALB/c pregnancies. Our results indicate that the extent of stimulation of maternal strain lymphocytes in response to stimulator placental cells in mixed lymphocyte-placenta reactions (MLPR) was much higher in the normal mating combination compared with the abortion- prone mating combination. Cytokine analysis of the supernatants from MLPR indicates that there is significantly higher production of TNF- alpha, IFN-gamma, and IL-2 in supernatants from the abortion-prone combination than in supernatants from the normal combination. Furthermore, MLPR-stimulated cells induce resorptions in normal pregnant mice; maternal strain lymphocytes stimulated by placentas from the abortion-prone combination induce high rates of fetal resorptions, but lymphocytes stimulated with placentas from the normal combination do not. Together, these results suggest that immunologically mediated fetal resorptions probably result from improper or inappropriate maternal responses to placental Ags. Our observations also suggest that such effects are probably mediated by cytokines.

This article has been cited by other articles:

				M. Takeda, H. Yamada, K. Iwabuchi, S. Shimada, M. Naito, N. Sakuragi, H. Minakami, and K. Onoe Administration of high-dose intact immunoglobulin has an anti-resorption effect in a mouse model of reproductive failure Mol. Hum. Reprod., November 1, 2007; 13(11): 807 - 814. [Abstract] [Full Text] [PDF]

				C. M. Constantin, D. Masopust, T. Gourley, J. Grayson, O. L. Strickland, R. Ahmed, and E. A. Bonney Normal Establishment of Virus-Specific Memory CD8 T Cell Pool following Primary Infection during Pregnancy J. Immunol., October 1, 2007; 179(7): 4383 - 4389. [Abstract] [Full Text] [PDF]

				V. Minas, U. Jeschke, S.N. Kalantaridou, D.U. Richter, T. Reimer, I. Mylonas, K. Friese, and A. Makrigiannakis Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin Mol. Hum. Reprod., September 1, 2007; 13(9): 663 - 673. [Abstract] [Full Text] [PDF]

				J. E. Boyson, N. Nagarkatti, L. Nizam, M. A. Exley, and J. L. Strominger Gestation stage-dependent mechanisms of invariant natural killer T cell-mediated pregnancy loss PNAS, March 21, 2006; 103(12): 4580 - 4585. [Abstract] [Full Text] [PDF]

				A. C. Zenclussen, K. Gerlof, M. L. Zenclussen, A. Sollwedel, A. Z. Bertoja, T. Ritter, K. Kotsch, J. Leber, and H.-D. Volk Abnormal T-Cell Reactivity against Paternal Antigens in Spontaneous Abortion: Adoptive Transfer of Pregnancy-Induced CD4+CD25+ T Regulatory Cells Prevents Fetal Rejection in a Murine Abortion Model Am. J. Pathol., March 1, 2005; 166(3): 811 - 822. [Abstract] [Full Text] [PDF]

				X.-Y. Zhu, Y.-H. Zhou, M.-Y. Wang, L.-P. Jin, M.-M. Yuan, and D.-J. Li Blockade of CD86 Signaling Facilitates a Th2 Bias at the Maternal-Fetal Interface and Expands Peripheral CD4+CD25+ Regulatory T Cells to Rescue Abortion-Prone Fetuses Biol Reprod, February 1, 2005; 72(2): 338 - 345. [Abstract] [Full Text] [PDF]

				A. Abou-Bacar, A. W. Pfaff, S. Georges, V. Letscher-Bru, D. Filisetti, O. Villard, E. Antoni, J.-P. Klein, and E. Candolfi Role of NK Cells and Gamma Interferon in Transplacental Passage of Toxoplasma gondii in a Mouse Model of Primary Infection Infect. Immun., March 1, 2004; 72(3): 1397 - 1401. [Abstract] [Full Text] [PDF]

				E. G. Olivares, R. Munoz, G. Tejerizo, M. J. Montes, F. Gomez-Molina, and A. C. Abadia-Molina Decidual Lymphocytes of Human Spontaneous Abortions Induce Apoptosis but Not Necrosis in JEG-3 Extravillous Trophoblast Cells Biol Reprod, October 1, 2002; 67(4): 1211 - 1217. [Abstract] [Full Text] [PDF]

				D. A. Terrone, B. K. Rinehart, J. P. Granger, P. S. Barrilleaux, J. N. Martin Jr, and W. A. Bennett Interleukin-10 Administration and Bacterial Endotoxin-Induced Preterm Birth in a Rat Model Obstet. Gynecol., September 1, 2001; 98(3): 476 - 480. [Abstract] [Full Text] [PDF]

				M. Imaizumi, A. Pritsker, M. Kita, L. Ahmad, P. Unger, and T. F. Davies Pregnancy and Murine Thyroiditis: Thyroglobulin Immunization Leads to Fetal Loss in Specific Allogeneic Pregnancies Endocrinology, February 1, 2001; 142(2): 823 - 829. [Abstract] [Full Text] [PDF]

				N. Hanna, I. Hanna, M. Hleb, E. Wagner, J. Dougherty, D. Balkundi, J. Padbury, and S. Sharma Gestational Age-Dependent Expression of IL-10 and Its Receptor in Human Placental Tissues and Isolated Cytotrophoblasts J. Immunol., June 1, 2000; 164(11): 5721 - 5728. [Abstract] [Full Text] [PDF]

				M. T. Long and T. V. Baszler Neutralization of Maternal IL-4 Modulates Congenital Protozoal Transmission: Comparison of Innate Versus Acquired Immune Responses J. Immunol., May 1, 2000; 164(9): 4768 - 4774. [Abstract] [Full Text] [PDF]

				M. Gorivodsky, I. Zemlyak, H. Orenstein, S. Savion, A. Fein, A. Torchinsky, and V. Toder TNF-{alpha} Messenger RNA and Protein Expression in the Uteroplacental Unit of Mice with Pregnancy Loss J. Immunol., May 1, 1998; 160(9): 4280 - 4288. [Abstract] [Full Text] [PDF]