Table 1.
CD4+ memory T cells in pregnancy.
| Memory T cell | Markers (human) | Cytokines | Findings in pregnancy | Findings in complications of pregnancy | |
|---|---|---|---|---|---|
| CD4+ | EM | CD45RO+, CD45RA−, CD44+, CCR7−, CD62L−, CD28+ | IFN-gamma+, TNF+, IL4+, IL5+ | - Higher proportion in peripheral blood in pregnancy (23, 30) - Higher proportions in decidua compared to peripheral blood (19, 31) - Increased IFN-gamma, IL4, PD-1, Tim-3, CTLA-4, and LAG-3 expression in decidua compared to peripheral blood (19) - Lower PD-1 expression in peripheral blood in pregnancy (23) - Higher proportion and higher activated proportion in peripheral blood postpartum compared to nulliparous women (30) |
- Comparable proportions in peripheral blood in preeclampsia and healthy controls (32) - Higher proportions in peripheral blood in women with recurrent miscarriages compared to healthy controls (not specified CD4/CD8) (33) |
| TEMRA | CD45RO−, CD45RA+, CCR7−, CD62L−, CD28− | Perforin+, granzyme B+ | Not studied in pregnancy | Not studied in complications of pregnancy | |
| CM | CD45RO+, CD45RA−, CD44+, CCR7+, CD62L+, CD28+ | IL2+, IFN-gamma−, and TNF− | - Higher proportion in peripheral blood compared to menstrual blood (31) - Comparable proportions and HLA-DR and CD38 expression in peripheral blood in non-pregnant and pregnant women (23, 30, 34) - Higher proportions in decidua compared to peripheral blood (31) - Higher proportion and higher activated proportion in peripheral blood postpartum compared to nulliparous women (30) |
- Higher proportion in peripheral blood in preeclampsia compared to healthy controls (32) - Comparable CD27, CD28, and CD127 expression in peripheral blood in preeclampsia and healthy controls (32) - Higher proportions in peripheral blood in women with recurrent miscarriages compared to healthy controls (not specified CD4/CD8) (33, 35) |
|
| TRM | CD45RO+, CD45RA−, CCR7−, CD62L−, CD69+/−, CD103+/− | IFN-gamma+, IL17+ | Not studied in pregnancy | Not studied in complications of pregnancy | |
| Treg memory | CD45RO+, CD45RA−, CD44+, CD25+, CD127−, Foxp3+, CTLA4+ | IL10+, TGFB+ | - Higher proportions in the decidua compared to peripheral blood (36) - Strong increase in peripheral blood in the first trimester (37) - Comparable proportions in peripheral blood in 3rd trimester and non-pregnant women (34) - Higher immune regulating capabilities upon stimulation with umbilical cord blood (36) - HLA-DR+ proportion in pregnancy showed decreased suppressive activity compared to HLA-DR+ proportion in non-pregnant women (37) - Differentiated from RTE Treg cells in first trimester peripheral blood (38) - Remain high during pregnancy, decreased with onset of labor, and at preconception levels postpartum (38) - In mice, paternal-specific Treg memory is generated in gestation, remaining at lower levels postpartum, and lowering resorption rates in a subsequent pregnancy (12, 39, 40) |
- Higher proportion in peripheral blood in preeclampsia compared to healthy controls (32) - Higher proportion of RTE Treg cells in peripheral blood in preeclampsia differentiate into CD31+ Treg memory cells (38). - CD31+ Treg memory cells in peripheral blood in preeclampsia have decreased immune suppressive capacity compared to CD31+ memory Treg cells in healthy women (38). - HLA-DR− memory Treg cells were increased in gestational diabetes with dietary adjustment (41) - HLA-DR− memory Treg cells were strongly increased in gestational diabetes with insulin therapy (41) |
|
| FHM | CXCR5+, CD45RA−, CD45RO+, CD62L+, CCR7+, FR4+ | IL21+, IL10+ | - Increased in the uterus and placenta toward late gestation in mice (42) | - Higher PD-1+CCR7+ and PD-1+ICOS+ proportions in decidual tissue but not in peripheral blood from spontaneous miscarriages compared to elective terminations in healthy controls (43) | |
| Memory stem cell | CD45RO−, CD45RA+, CCR7+, CD62L+, CD28+, CD27+, CD95+, IL2RB+ | IFN-gamma−, IL2+/− | Not studied in pregnancy | Not studied in complications of pregnancy | |
EM, effector memory; TEMRA, effector memory CD45RA revertant; CM, central memory; TRM, tissue resident memory; Treg, T regulatory; FHM, follicular helper memory; CCR7, CC-chemokine receptor 7; CD62-L, L-selectin; Foxp3, forkhead box P3; CXCR5, chemokine receptor type 5; FR4, folate receptor-4; IFN-gamma, interferon-gamma; TNF, tumor necrosis factor; IL, interleukin; TGFB, transforming growth factor B; PD-1, programmed death-1; Tim-3, T cell immunoglobulin and mucin domain 3; CTLA-4, cytotoxic T lymphocyte antigen; LAG-3, lymphocyte activation gene 3; HLA-DR, Human Leukocyte Antigen-DR; ICOS, inducible T cell co-stimulator; RTE, recent thymic emigrant.