Stronger T-Cell Alloreactivity and Diminished Suppressive Capacity of Peripheral Regulatory T Cells in Infertile Women Undergoing In Vitro Fertilization.
OBJECTIVE
Increasing evidence suggests modulation of the maternal immune response to be essential for successful pregnancy. We studied the immunophenotypic profile and function of peripheral blood T lymphocytes in infertile women undergoing in vitro fertilization (IVF) and fertile control population.


METHODS
We collected peripheral blood mononuclear cells (PBMC) from infertile patients with recurrent implantation failure (RIF), infertile patients with successful IVF (IVFs), and normal fertile women. Cells were phenotypically analyzed, and the proliferative response and cytokine production were studied in mixed lymphocyte cultures (MLC), using lymphocytes of the own partner, or a third-party male as stimulators cells. To examine the suppressive capacity of regulatory regulatory T cells (Tregs), we performed MLC studies with a CD45(+) fraction depleted for CD4(+) CD25(bright) T cells.


RESULTS
No significant differences in proportions of subsets of circulating T lymphocytes were observed. The proliferative allo-immune response of PBMC of IVF women (RIF and IVFs) was significantly higher, with higher production of T-helper cells (Th1) and Th2 cytokines, compared to the fertile women. This difference in proliferation and cytokine production was associated with a diminished suppressive capacity of Tregs in these women.


CONCLUSIONS
The higher allo-immune response of the IVF women compared to fertile women might be the result of a diminished suppressive capacity of Tregs and emphasizes the important role of Tregs during conception.
Department of Gynecology and Obstetrics, Leiden University Medical Centre, Leiden, The Netherlands.
Lisa E E L O
LE
Lashley
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
Carin
C
van der Keur
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
Els
E
van Beelen
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
Rowena
R
Schaap
Department of Gynecology and Obstetrics, Leiden University Medical Centre, Leiden, The Netherlands.
Lucette A J
LA
van der Westerlaken
Department of Obstetrics, UMCG, Groningen, The Netherlands.
Sicco A
SA
Scherjon
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
Frans H J
FH
Claas
D000328:Adult; D049109:Cell Proliferation; D010064:Embryo Implantation / Q000276:immunology; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007247:Infertility, Female / Q000276:immunology* / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
Human leukocyte antigen; T lymphocytes; in vitro fertilization; regulatory T cells; suppressive capacity