Human decidual tissue contains differentiated CD8+ effector-memory T cells with unique properties.
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.
Tilburgs
Tamara
T
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Tilburgs@FAS.Harvard.edu
Schonkeren
Dorrith
D
Eikmans
Michael
M
Nagtzaam
Nicole M
NM
Datema
Gert
G
Swings
Godelieve M
GM
Prins
Frans
F
van Lith
Jan M
JM
van der Mast
Barbara J
BJ
Roelen
Dave L
DL
Scherjon
Sicco A
SA
Claas
Frans H
FH
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
D054353:Perforin; D053804:Granzymes