T lymphocytes, are part of the adaptive immune system and play a central role in reproductive immunology¹. T cells can be separated into three major groups based on their function: cytotoxic T cells (CTLs), T helper cells (T_H), and regulatory T cells (T_REGs). Differential expression of cell surface markers and cytokine secretion profiles provide valuable information about the phenotype and functional behavior of T cells during pregnancy, in which T cells help regulate the fine balance between host defense and maternal-fetal tolerance.

The several subsets of T cells each possess a distinct set of functions. CD8⁺ CTLs destroy infected target cells through the release of perforin and granzymes and are implicated in transplant rejection. CD4⁺ T_H cells have little cytotoxic activity but secrete different cytokines to facilitate other leukocytes such as B cells, macrophages, and neutrophils in the immune response against pathogens (e.g. viruses, allergies, bacteria and fungi). Three distinct CD4⁺ T_H cell subsets can be defined based on their expression of transcription factors, signature cytokines, and cell surface markers. T_H1 cells are identified by T-bet, IFNγ, CXCR3 and CCR5; T_H2 cells are identified by GATA-3, IL-4 and CCR4; and T_H17 cells are identified by RORγt, IL-17 and CCR6. Finally, T_REGs are crucial for the maintenance of immunological tolerance. They are defined by the expression of the transcription factor FoxP3, cytokine IL-10 and TFG-β, and high expression levels of the IL-2 receptor, CD25. IQ Products can help your research with antibodies against several of these markers, which are highlighted in the table below.

T cells are an important cell population within the decidua over the course of pregnancy^{2, 3}. This T cell population comprises of specialized decidual T cells in addition to the above mentioned subsets. The majority of decidual T cells represent antigen experienced effector T cells (CD45RA^– or CD45RO⁺)^{4, 5}. Decidual T cells differ from peripheral T cells by the expression of activation markers such as CD69, HLA-DR, and CD25⁶. Furthermore, in the uterine environment, there is an inverse CD4/CD8 ratio and an altered distribution of T_H1, T_H2, and T_H17 cells compared to the peripheral blood^{5, 7}. In addition, during pregnancy T_REG cells are enriched at the maternal-fetal interface and important for maintaining fetal tolerance and suppressing decidual T cell effector responses. Imbalances of the T_H1, T_H2, T_H17, and T_REG cell distributions are associated with pregnancy complications such as, preterm birth (PTB)⁸, pre-eclampsia (PE)⁹, and (unexplained) recurrent pregnancy loss (RPL)¹⁰. Therefore, a tight immune regulation of CD4⁺ T_H cells (i.e. T_H1, T_H2, and T_H17), T_REGs, and CTLs is paramount for a successful pregnancy outcome.

To support the use of flow cytometry for studying the complexity of immune cells during pregnancy, IQ Products offers various important cell surface markers, cytokines, and stimulation reagents to identify and stimulate T cells, highlighted in the table below. Are you interested in other markers, different fluorochromes or need help creating a panel for your research purpose? Contact us at techsupport@iqproducts.nl

References

• Nancy, P., et al. T cell behavior at the maternal-fetal interface. The International journal of developmental biology 58, 189–198, doi:10.1387/ijdb.140054ae (2014).

• Tilburgs, T., et al. Expression of NK cell receptors on decidual T cells in human pregnancy. Journal of reproductive immunology 80,22–32, doi:10.1016/j.jri.2009.02.004 (2009).

• Williams, P. J., et al. 2009. Decidual leucocyte populations in early to late gestation normal human pregnancy. J. Reprod. Immunol. 82: 24–31.

• Saito, S., et al. (1994). A study of CD45RO, CD45RA and CD29 antigen expression on human decidual T cells in an early stage of pregnancy. Immunol Lett 40: 193-197.

• Tilburgs, T., et al. (2010b). Human decidual tissue contains differentiated CD8+ effector-memory T cells with unique properties. J Immunol 185: 4470-4477.

• Saito, S., et al. Expression of activation antigens CD69, HLA-DR, interleukin-2 receptor-alpha (IL-2R alpha) and IL-2R beta on T Cells of human decidua at an early stage of pregnancy. Immunology 75, 710–712 (1992).

• Feyaerts D., et al. Human uterine lymphocytes acquire a more experienced and tolerogenic phenotype during pregnancy. Scientific Reports. 2017;7(1):p. 2884. doi: 10.1038/s41598-017-03191-0.

• Koucky M., et al. Low levels of circulating T-regulatory lymphocytes and short cervical length are associated with preterm labor. J Reprod Immunol 2014; 106:110–7. 22

• Vargas-Rojas M.I., et al. Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia. J Matern Fetal Neonatal Med 2015; 29:1642–5.

• Wang W.J., et al. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol 2010; 84:164–70.