Immune cell profiling in normal pregnancy, partial and complete molar pregnancy.
OBJECTIVE
Cytotoxic T cells (Tc) and natural killer (NK) cells may play a role in controlling trophoblast invasion. This study was undertaken to determine the level of infiltration and antigen profile of immune cells and explore their relationship in normal placenta (NP) and molar tissues to better understand the biology of gestational trophoblastic diseases.


METHODS
Immunolocalization of CD8, Granzyme B (GrB), and FoxP3 was performed on sections prepared from 11 gestational age-matched NP, 19 partial moles (PM), and 18 complete moles (CM) to characterize effector (GrB+CD8+) and GrB- (GrB-CD8+) Tc cells, GrB+ NK cells (GrB+CD8-), and Treg (FoxP3+) cells.


RESULTS
Immune cells infiltrated into the implantation site of normal placenta, PM, and CM with increasing frequency. Effector and GrB- Tc, GrB+ NK and Treg infiltration in the CM were significantly stronger than seen in the normal placenta (p=0.002, p=0.007, p=0.002, respectively). Immune cell infiltration was not detected in the villi or trophoblast of gestational tissues. Treg infiltration in the implantation site was only observed in PM and CM. In CM and PM Tc infiltration positively correlated with Treg infiltration (p=0.035), but Treg infiltration did not correlate with the Tc effector ratio (effector Tc cells/all Tc cells).


CONCLUSIONS
In CM the cellular immune response in the implantation site was significantly more vigorous than seen in normal placenta. These observations demonstrate that in the implantation site of CM, the number of effector Tc and GrB+ NK cells are increased and Treg cells may negatively regulate T lymphocyte activation.
Nagymanyoki
Zoltan
Z
Division of Gynecologic Oncology, New England Trophoblastic Disease Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Callahan
Michael J
MJ
Parast
Mana M
MM
Fulop
Vilmos
V
Mok
Samuel C
SC
Berkowitz
Ross S
RS
D000328:Adult; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D053804:Granzymes / Q000032:analysis; D006801:Humans; D006828:Hydatidiform Mole / Q000737:chemistry / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D011247:Pregnancy / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014594:Uterine Neoplasms / Q000737:chemistry / Q000276:immunology*
D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053804:Granzymes