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Detection of a2V‐ATPase in T regulatory cells of women with recurrent spontaneous abortions or implantation failures
Author(s) -
Ntrivalas EI,
Fukui A,
GilmanSachs A,
Levine R,
KwakKim J,
Beaman KD
Publication year - 2006
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.2006.00383_27.x
Subject(s) - il 2 receptor , atpase , chemistry , treg cell , microbiology and biotechnology , immune system , immunology , medicine , biology , biochemistry , t cell , enzyme
Problem: T regulatory cells (Tregs) have recently been shown to play a critical role in maternal tolerance to the fetus. Tregs are decreased in women with recurrent miscarriages. a2V‐ATPase (previously referred to as Regeneration and Tolerance Factor) is expressed in activated lymphocytes and plays a role in immune regulation. The aim of this study was to investigate the expression of a2V‐ATPase on CD4 + /CD25 bright Tregs. Method of Study: Whole blood from women with RSA or implantation failures was reacted with anti‐CD4 and anti‐CD25 mAbs for the identification of CD4 + /CD25 bright and CD4 + /CD25 neg T cells by flow cytometric analysis. Subsequently, these two T‐cell populations were analyzed for the expression of a2V‐ATPase using PE‐conjugated 2C1 mAb (specific for the membrane portion of a2V‐ATPase). These two cell populations were also analyzed for the expression of CD71, CD62L, CD45RO and CD58 (Treg markers). Results: a2V‐ATPase was more highly expressed on CD4 + /CD25 bright Tregs (22.8 ± 16.4%) than on CD4 + /CD25 neg T cells (2.4 ± 3.8%) in women with RSA ( P < 0.0001). Additionally, a2V‐ATPase was more highly expressed on CD4+/CD25 bright Tregs (18.0 ± 18.2%) than on CD4+/CD25 neg T cells (1.5 ± 1.4%) in women with implantation failures ( P < 0.0001). a2V‐ATPase expression also coincided with the expression of CD71, CD62L, CD45RO and CD58 in Tregs, as opposed to the conventional CD4 + /CD25 neg T cells. Conclusions: The expression of a2V‐ATPase in Tregs of women with RSA or implantation failures is a novel finding and suggests that this vacuolar ATPase plays an important role in suppression. a2V‐ATPase may be a unique molecule in the identification of Tregs among peripheral blood lymphocytes and may also explain the tolerogenic activity of these cells.