title: The immunology of pregnancy: regulatory T cells control maternal immune tolerance toward the fetus.
abstract: Establishment and maintenance of pregnancy represents a challenge for the maternal immune system since it has to defend against pathogens and tolerate paternal alloantigens expressed in fetal tissues. Regulatory T (Treg) cells, a subset of suppressor CD4(+) T cells, play a dominant role in the maintenance of immunological self-tolerance by preventing immune and autoimmune responses against self-antigens. Although localized mechanisms contribute to fetal evasion from immune attack, in the last few years it has been observed that Treg cells are essential in promoting fetal survival avoiding the recognition of paternal semi-allogeneic tissues by maternal immune system. Several functional studies have shown that unexplained infertility, miscarriage and pre-clampsia are often associated with deficit in Treg cell number and function while normal pregnancy selectively stimulates the accumulation of maternal forkhead-box-P3(+) (FoxP3(+)) CD4(+) Treg cells with fetal specificity. Some papers have been reported that the number of Treg cells persists at elevated levels long after delivery developing an immune regulatory memory against father's antigens, moreover these memory Treg cells rapidly proliferate during subsequent pregnancies, however, on the other hand, there are several evidence suggesting a clear decline of Treg cells number after delivery. Different factors such as cytokines, adipokines, pregnancy hormones and seminal fluid have immunoregulatory activity and influence the success of pregnancy by increasing Treg cell number and activity. The development of strategies capable of modulating immune responses toward fetal antigens through Treg cell manipulation, could have an impact on the induction of tolerance against fetal antigens during immune-mediated recurrent abortion.
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, via Pansini 5, 80131 Napoli, Italy; Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), via Pansini 5, 80131 Napoli, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: La Rocca
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), via Pansini 5, 80131 Napoli, Italy.
authors.forename: Fortunata
authors.initials: F
authors.lastname: Carbone
authors.affiliation: Medical Department, Merck Serono S.p.A., Roma, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Longobardi
authors.affiliation: Dipartimento di Medicina e Chirurgia, Università degli Studi di Salerno, Baronissi Campus, via S. Allende, 84081 Baronissi Salerno, Italy; IRCCS MultiMedica, via Milanese 300, Sesto San Giovanni, 20099 Milano, Italy. Electronic address: gmatarese@unisa.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000276:immunology*; D054502:Histocompatibility, Maternal-Fetal / Q000276:immunology; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D056747:Immunomodulation; D051379:Mice; D011247:Pregnancy; D012661:Semen / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D006728:Hormones
keywords: Immune tolerance; Pregnancy; Recurrent miscarriage; Regulatory T cells