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Published online before print October 4, 2005
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*Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Canada; Biological Sciences, Efoa/Ceufe, Alfenas, MG, Brazil; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts; and Department of Anatomy and Cell Biology, Queen’s University, Kingston, Ontario, Canada
@ To whom correspondence should be addressed. E-mail: ctayade{at}uoguelph.ca.
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Abstract |
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During human and rodent uterine decidualization, transient but abundant numbers of uterine natural killer (uNK) cells appear, proliferate, and differentiate. uNK cells share features with peripheral NK cells but are specialized to promote interferon-
(IFN-)-mediated, pregnancy-associated, structural changes in maternal placental arteries. In CD8+ T cells and NK cells, the transcription factors T-bet and eomesodermin (Eomes) regulate maturation and effector functions, including IFN- production. No studies are reported for uNK cells. Implantation sites in T-bet null mice, which have a defect in NK cell maturation, had uNK cells normal in morphology and number and normally modified spiral arteries. As Eomes null mice are not viable, real-time polymerase chain reaction comparisons between C57Bl/6J (B6) and alymphoid (Rag20/0c0/0) mice were used to assess uNK cell expression of T-bet, Eomes, and the target genes IFN-, granzyme A, and perforin. Gestation dated (gd) uterine tissues (mixed cell composition) and 200 morphologically homogeneous, laser-capture, microdissected uNK cells of different maturation stages were used. In uterus, Eomes transcripts greatly outnumbered those of T-bet, whether donors were nonpregnant or pregnant, and increased to gd10. In uNK cells, transcripts for T-bet, Eomes, and IFN- were most abundant in mature stage cells, and transcripts for granzyme A and perforin were lower at this stage than in immature or senescent cells. Thus, Eomes dominance to T-bet discriminates regulation of the uNK cell subset from that observed for peripheral NK cells.
Key Words:
cell differentiation • granzyme • interferon- • perforin • reproductive immunology • transcription factors
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