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Immunological Puzzle Related to Recurrent Miscarriage: Overview

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The maternal immune-system must be modified in order to tolerate the semi-allogeneic conceptus. Because maternal alloreactive lymphocytes are not depleted, local mechanisms have to play a key role in altering the immune response. Both humoral and cellular immunity are affected. Th1/Th2 cytokine balance is not essential to have normal pregnancies. Alloreactive Th1 cells must be regulated, for instance, by regulatory T cells. Animal and human experiments showed that Treg number and/or function are diminished in spontaneous abortions. Miscarriage can be prevented by transfer of Treg from normal pregnant mice. Treg at the maternal-fetal interface avoid fetal allo-rejection by means of the creation of a “tolerant” microenvironment characterized by expression of IL-10, TGF-β, HO-1 and IDO, rather than diminishing the Th1 cytokines. Treg or CTLA-4 expression on Treg enhances IDO expression. T-regFoxp3+ can increase placental HO-1. In turn, HO-1 may lead to up-regulation of TGF-β, IL-10 and CTLA-4. The role of progesterone, β-HCG and hPGH and their relation to uNK cell and Treg activity are discussed. A new linking between trophoblast apoptosis, Treg, aPL and NK cell is also raised. Finally, a relationship between HLA-haplotypes and HLA-G molecule, Babs, NK cells, Th1/Th2/Th3/Tr1/Treg balance, aPL and cytotoxic TCD8+, CD4+ is discussed.

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Keywords: NK cells; Recurrent miscarriages; Treg lymphocytes; antiphospholipid antibodies; blocking antibodies; cytokines

Document Type: Research Article

Publication date: August 1, 2009

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  • Current Immunology Reviews publishes frontier reviews on all the latest advances in clinical immunology. The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians in clinical immunology.
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