The immunomodulating effect of seminal plasma on T cells

Meuleman, Tess; Snaterse, Gido; Beelen, Els van; Anholts, JDH; Pilgram, Gonneke S. K.; Westerlaken, Lucette A. J. van der; Eikmans, Michael; Claas, Frans H.J.

doi:10.1016/j.jri.2015.01.012

Cited by 28 publications

(23 citation statements)

References 35 publications

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“…The immunoregulatory role of seminal plasma is not exclusive to rodents. Exposure of human peripheral blood T cells to seminal plasma in vitro led to increased mRNA expression of CD25, IL‐10 and FoxP3, which was partly dependent on the presence of APCs . These results suggest that seminal plasma contains immunomodulatory factors that may contribute to the formation of a tolerogenic environment at the embryo implantation site and that exposure to seminal fluid at mating promotes a state of functional tolerance‐mediated by expansion of the local antigen‐specific Treg pool.…”

Section: Tregs In Normal Pregnancymentioning

confidence: 83%

“…These results suggest that seminal plasma contains immunomodulatory factors that may contribute to the formation of a tolerogenic environment at the embryo implantation site and that exposure to seminal fluid at mating promotes a state of functional tolerance‐mediated by expansion of the local antigen‐specific Treg pool. One of these immune modulating aspects in semen could be soluble HLA (sHLA), as human seminal plasma contains sHLA‐G and sHLA class I . HLA‐G inhibits the proliferation and cytotoxic functions of T cells and induces immunosuppressive T cells .…”

Section: Tregs In Normal Pregnancymentioning

confidence: 99%

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What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages?

Craenmehr

Heidt

Eikmans

et al. 2016

HLA

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Couples of whom the woman has had a miscarriage have two major concerns: the cause and possible risk of recurrence. Unfortunately, a significant proportion of cases of recurrent miscarriage (RM) remain unexplained despite detailed investigation. Because data suggest that regulatory T cells (Treg) are involved in the maternal acceptance of the allogeneic foetus, RM could possibly be explained by a disturbance of the Treg network. The possible role of Tregs in RM is described in this review, as well as their potential application in diagnostics and therapeutic intervention trials.

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Section: Tregs In Normal Pregnancymentioning

confidence: 83%

Section: Tregs In Normal Pregnancymentioning

confidence: 99%

What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages?

Craenmehr

Heidt

Eikmans

et al. 2016

HLA

Self Cite

View full text Add to dashboard Cite

show abstract

“…Extensive studies in mice show Tregs arise after mating when seminal fluid delivers paternal alloantigens in the context of high concentrations of the potent Treginducing factor TGF-b (24)(25)(26). Similar responses occur in women in which both in vivo and in vitro studies implicate seminal fluid in priming Tregs to enable tolerance to conceptus Ags (27)(28)(29).…”

mentioning

confidence: 95%

Thymus-Derived Regulatory T Cells Exhibit Foxp3 Epigenetic Modification and Phenotype Attenuation after Mating in Mice

Moldenhauer

Schjenken

Hope

et al. 2019

The Journal of Immunology

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Regulatory T cells (Tregs) are essential for maternal tolerance in allogeneic pregnancy. In preeclampsia, Tregs are fewer and display aberrant phenotypes, particularly in the thymic Treg (tTreg) compartment, potentially because of insufficient priming to male partner alloantigens before conception. To investigate how tTregs as well as peripheral Tregs (pTregs) respond to male partner seminal fluid, Foxp3 + CD4 + Tregs were examined in the uterus and uterus-draining lymph nodes in virgin estrus mice and 3.5 d postcoitum. Mating elicited 5-fold increases in uterine Tregs accompanied by extensive Treg proliferation in the uterusdraining lymph nodes, comprising 70% neuropilin 1 + tTregs and 30% neuropilin 1 2 pTregs. Proliferation marker Ki67 and suppressive competence markers Foxp3 and CTLA4 were induced after mating in both subsets, and Ki67, CTLA4, CD25, and GITR were higher in tTregs than in pTregs. Analysis by t-stochastic neighbor embedding confirmed phenotypically distinct tTreg and pTreg clusters, with the proportion of tTregs but not pTregs among CD4 + T cells expanding in response to seminal fluid. Bisulphite sequencing revealed increased demethylation of the Treg-specific demethylation region in the Foxp3 locus in tTregs but not pTregs after mating. These data show that tTregs and pTregs with distinct phenotypes both respond to seminal fluid priming, but the Foxp3 epigenetic signature is uniquely increased in tTregs. We conclude that reproductive tract tTregs as well as pTregs are sensitive to local regulation by seminal fluid, providing a candidate mechanism warranting evaluation for the potential to influence preeclampsia susceptibility in women.

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“…Previous in vitro studies reported an opposite effect of SP exposure on lymphocyte immunity (36, 37). Indeed, it has been shown that SP downregulated T cell and NK cell functions, such as cytotoxicity and cytokine production.…”

Section: Discussionmentioning

confidence: 83%

Seminal Plasma Exposures Strengthen Vaccine Responses in the Female Reproductive Tract Mucosae

et al. 2019

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HIV-1 sexual transmission occurs mainly via mucosal semen exposures. In the female reproductive tract (FRT), seminal plasma (SP) induces physiological modifications, including inflammation. An effective HIV-1 vaccine should elicit mucosal immunity, however, modifications of vaccine responses by the local environment remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized the impact of HIV-1+ SP intravaginal exposure on the local immune responses of non-human primates. Multiple HIV-1+ SP exposures did not impact the anti-MVA antibody responses. However, SP exposures revealed an anti-MVA responses mediated by CD4+ T cells, which was not observed in the control group. Furthermore, the frequency and the quality of specific anti-MVA CD8+ T cell responses increased in the FRT exposed to SP. Multi-parameter approaches clearly identified the cervix as the most impacted compartment in the FRT. SP exposures induced a local cell recruitment of antigen presenting cells, especially CD11c+ cells, and CD8+ T cell recruitment in the FRT draining lymph nodes. CD11c+ cell recruitment was associated with upregulation of inflammation-related gene expression after SP exposures in the cervix. We thus highlight the fact that physiological conditions, such as SP exposures, should be taken into consideration to test and to improve vaccine efficacy against HIV-1 and other sexually transmitted infections.

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The immunomodulating effect of seminal plasma on T cells

Cited by 28 publications

References 35 publications

What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages?

What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages?

Thymus-Derived Regulatory T Cells Exhibit Foxp3 Epigenetic Modification and Phenotype Attenuation after Mating in Mice

Seminal Plasma Exposures Strengthen Vaccine Responses in the Female Reproductive Tract Mucosae

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