Pregnancy can induce long-persisting primed CTLs specific for inherited paternal HLA antigens

Kampen, Corine A. van; Maarschalk, Minke F. J. Versteeg-van der Voort; Langerak-Langerak, Janneke; Beelen, Els van; Roelen, Dave L.; Claas, Frans H.J.

doi:10.1016/s0198-8859(01)00209-9

Cited by 89 publications

(55 citation statements)

References 30 publications

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“…Interestingly, Treg suppressed IL-4 secretion against paternal but not unrelated alloantigens during pregnancy. In transplantation studies, it was described that antigen-specific cytotoxic T lymphocytes (Tctl) are directed against fetal inherited paternal alloantigen such as HLA 42 and minor antigens. 43 By analyzing peripheral blood cells from 17 minor H antigen-disparate mother-offspring pairs, van Halteren and colleagues 44 observed that both antigenspecific CD8 + CTLs (cytotoxic T lymphocytes) and CTLA-4-dependent CD8 + Treg are able to emerge during pregnancy and persist over time when mother and offspring differ on minor histocompatibility antigens.…”

Section: Generation Of Treg In Pregnancy and Antigen Specificitymentioning

confidence: 99%

REVIEW ARTICLE: Regulatory T Cells and Their Role in Pregnancy

Leber

Teles

Zenclussen

2010

American J Rep Immunol

148

116

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Citation Leber A, Teles A, Zenclussen AC. Regulatory T cells and their role in pregnancy. Am J Reprod Immunol 2010Regulatory T cells emerge in the last years as key players in allowing fetal survival within the maternal uterus. They were shown to be a unique subpopulation of T cells expanding during human and murine pregnancy. The importance of Treg for a normal pregnancy situation was proven by studies showing that their absence impairs murine pregnancy while the adoptive transfer of Treg prevents fetal rejection. In humans, pregnancy pathologies are associated with lower Treg frequencies while therapies that improve pregnancy outcome are able to boost their number. Functional studies have shown that Treg can regulate immune cell responses directly at the fetal–maternal interface either by interacting with other cells or by inducing the expression of immune regulatory molecules. This article revises relevant literature on regulatory T cells in human and murine pregnancy.

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Section: Generation Of Treg In Pregnancy and Antigen Specificitymentioning

confidence: 99%

REVIEW ARTICLE: Regulatory T Cells and Their Role in Pregnancy

Leber

Teles

Zenclussen

2010

American J Rep Immunol

148

116

View full text Add to dashboard Cite

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“…Although pregnancy frequently results in activation of maternal B cells 1 and T CTL directed against fetal inherited paternal alloantigen, such as HLA 2 and minor H antigens, 3 not all parous women develop cytolytic activity against the latter alloantigens. 3 Importantly, long-lasting tolerance may also be induced in offspring exposed to noninherited maternal alloantigen (NIMA), such as rhesus D 4 or HLA.…”

Section: Introductionmentioning

confidence: 99%

Naturally acquired tolerance and sensitization to minor histocompatibility antigens in healthy family members

Halteren

Jankowska‐Gan

Joosten

et al. 2009

Blood

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Bidirectional cell transfer during pregnancy frequently leads to postpartum persistence of allogeneic cells and alloimmune responses in both the mother and in her offspring. The life-long consequences of naturally acquired alloimmune reactivity are probably of importance for the outcome of allogeneic stem cell transplantation. We investigated the presence of CD8 pos minor histocompatibility (H) antigen-specific cytotoxic T lymphocytes (T CTL ) and CD8 pos minor H antigen-specific T regulator cells (T REG ) in peripheral blood cells obtained from 17 minor H antigen-disparate mother-offspring pairs. Absence of minor H antigen-specific T REG , as marked by the feasibility to expand T CTL from isolated tetramer pos populations, was observed in 6 mothers and 1 son. The presence of minor H alloantigen-specific T REG was observed in 4 mothers and 5 sons.These T REG were detected within isolated tetramer dim staining fractions and functioned in a CTLA-4-dependent fashion. Our study indicates that both T CTL and T REG mediated alloimmunity against minor H antigens may be present in healthy female and male hematopoietic stem cell donors, potentially influencing graftversus-host reactivity in different ways.

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“…Contemporary studies confirm that activated T cells reactive with fetal HLA are detectable in the peripheral blood and decidua of pregnant women and are consistent with healthy pregnancy (Tilburgs et al, 2009, van Kampen et al, 2001 numbers of these cells (Lashley et al, 2013). Mice with transgenic T cells reactive to conceptus antigens conclusively demonstrate that immune awareness of fetal antigens occurs, and begins from the time of conception, with T cell responses ranging from activation and proliferation to anergy and deletion (Moldenhauer et al, 2010a).…”

Section: Immune Recognition Of Pregnancy Commences Before Implantationmentioning

confidence: 88%

Immunological determinants of implantation success

Robertson

Moldenhauer²

2014

Int. J. Dev. Biol.

110

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The capacity of the immune system to maintain the integrity of the individual requires recognition and control of entities identified as genetically distinct, or 'non-self' . In mammalian reproduction, the embryo and subsequent fetus and placenta are all recognized as non-self by the maternal immune system, and are vulnerable to immunological attack. An active system to prevent rejection must exist from when conceptus and maternal tissues first come into contact at implantation.

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Pregnancy can induce long-persisting primed CTLs specific for inherited paternal HLA antigens

Cited by 89 publications

References 30 publications

REVIEW ARTICLE: Regulatory T Cells and Their Role in Pregnancy

REVIEW ARTICLE: Regulatory T Cells and Their Role in Pregnancy

Naturally acquired tolerance and sensitization to minor histocompatibility antigens in healthy family members

Immunological determinants of implantation success

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