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Updated: Aug 13, 2026
Isolation of Leukocytes from the Human Maternal-fetal Interface
Published on: May 21, 2015
Phenotypic and functional cellular differences between human CD3- decidual and peripheral blood leukocytes
G Deniz1, S E Christmas, R Brew
1Department of Immunology, University of Liverpool, UK.
Insights
Decidual granulated leukocytes (DGL) exhibit natural killer (NK) cell activity, effectively targeting HLA-negative cells. However, HLA-G expression on target cells can inhibit DGL-mediated killing, and DGL may suppress allogeneic immune responses.
Area of Science:
- Immunology
- Cell Biology
- Reproductive Immunology
Background:
- Human decidualized endometrial tissue contains CD3- leukocyte clones with distinct phenotypes compared to peripheral blood lymphocyte (PBL) clones.
- These decidual granulated leukocyte (DGL) clones possess natural killer (NK) cell activity, but their functional characteristics, particularly in relation to target cell expression of MHC molecules, require detailed investigation.
Purpose of the Study:
- To compare the characteristics of CD3- DGL clones with CD3- PBL clones.
- To investigate the NK cell activity of DGL clones against various target cells, including those expressing specific HLA molecules.
- To examine the immunomodulatory effects of DGL on mixed lymphocyte reactions (MLR).
Main Methods:
- Isolation and characterization of CD3- leukocyte clones from human decidualized endometrial tissue and peripheral blood.
- Assessment of cytotoxic activity against NK-resistant cell lines and target cells with varying HLA expression.
- Evaluation of the effects of CD3- DGL on one-way mixed lymphocyte reactions (MLR).
Main Results:
- CD3- DGL clones were predominantly CD16- CD56+, unlike CD3- PBL clones (mostly CD16+ CD56+).
- Both DGL and PBL clones displayed MHC-nonrestricted NK cell activity.
- CD3- DGL clones showed potent cytotoxicity against HLA-negative cells, but HLA-G expression on target cells reduced killing. DGL also suppressed MLR.
Conclusions:
- CD3- DGL clones possess significant MHC-nonrestricted cytotoxic activity, particularly against HLA-deficient cells.
- Expression of HLA-G by target cells confers protection against DGL-mediated lysis.
- CD3- DGL may play a role in immune suppression within the maternal-fetal interface, potentially modulating allogeneic responses.
Abstract:
CD3- leukocyte clones derived from human decidualized endometrial tissue of first trimester pregnancy have been compared with CD3- PBL clones. Most CD3- decidual granulated leukocyte (DGL) clones were CD16- CD56+, whereas most CD3- PBL clones were CD16+ CD56+. CD3- DGL and PBL clones, whether CD16+ or not, showed MHC-nonrestricted NK cell activity. However, CD3- CD16- DGL clones had low cytotoxic activity against the NK-resistant cell line BSM, whereas CD3- CD16+ DGL and CD3- PBL clones were strongly cytotoxic. Cytolytic activity has also been investigated in respect of target cell HLA-G expression, because this nonpolymorphic class I MHC molecule is expressed selectively by invasive fetal cytotrophoblast. Class I HLA Ag loss cell mutants were killed efficiently by CD3- DGL clones. Expression of transfected HLA-B8 increased their sensitivity to lysis by most CD3- DGL clones, whereas expression of transfected HLA-G commonly led to decreased target cell killing. In addition, the effects of uncloned CD3- DGL on the one-way MLR have been examined. These cells were very poor responders and, unless cultured to induce expression of class II MHC molecules, were also very poor stimulators. When fresh CD3- DGLs were added as third-party cells, either autologous or allogeneic to responder cells, [3H]TdR incorporation was decreased in the MLR. Thus, CD3- DGL clones express MHC-nonrestricted cytolytic activity, notably against HLA-negative cells, but expression of HLA-G offers protection to target cells. In addition, CD3- DGL may function to suppress allogeneic responses.
