title: Human decidual tissue contains differentiated CD8+ effector-memory T cells with unique properties.
abstract: During pregnancy, maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Recently, CD4(+)CD25(bright) regulatory T cells have been shown to be concentrated in decidual tissue, where they are able to suppress fetus-specific and nonspecific immune responses. Decidual CD8(+) T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal-maternal interface, but data on the characteristics of these cells are limited. In this study we examined the decidual and peripheral CD8(+) T cell pool for CD45RA, CCR7, CD28, and CD27 expression, using nine-color flow cytometry. Our data demonstrate that decidual CD8(+) T cells mainly consist of differentiated CD45RA(-)CCR7(-) effector-memory (EM) cells, whereas unprimed CD45RA(+)CCR7(+) naive cells are almost absent. Compared with peripheral blood EM CD8(+) T cells, the decidual EM CD8(+) T cells display a significantly reduced expression of perforin and granzyme B, which was confirmed by immunohistochemistry of decidual tissue sections. Interestingly, quantitative PCR analysis demonstrates an increased perforin and granzyme B mRNA content in decidual EM CD8(+) T cells in comparison with peripheral blood EM CD8(+) T cells. The presence of high levels of perforin and granzyme B mRNA in decidual EM T cells suggests that decidual CD8(+) T cells pursue alternative means of EM cell differentiation that may include a blockade of perforin and granzyme B mRNA translation into functional perforin and granzyme B proteins. Regulation of decidual CD8(+) T cell differentiation may play a crucial role in maternal immune tolerance to the allogeneic fetus.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Tilburgs@FAS.Harvard.edu
authors.forename: Tamara
authors.initials: T
authors.lastname: Tilburgs
authors.forename: Dorrith
authors.initials: D
authors.lastname: Schonkeren
authors.forename: Michael
authors.initials: M
authors.lastname: Eikmans
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Nagtzaam
authors.forename: Gert
authors.initials: G
authors.lastname: Datema
authors.forename: Godelieve M
authors.initials: GM
authors.lastname: Swings
authors.forename: Frans
authors.initials: F
authors.lastname: Prins
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Lith
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: van der Mast
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Sicco A
authors.initials: SA
authors.lastname: Scherjon
authors.forename: Frans H
authors.initials: FH
authors.lastname: Claas
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D003656:Decidua / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D007108:Immune Tolerance; D007150:Immunohistochemistry; D054353:Perforin / Q000096:biosynthesis; D011247:Pregnancy / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D054353:Perforin; D053804:Granzymes