Plasticity and flexibility of T cells in human pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 149-149

• Introduction:Pregnancy challenges the immune system. Thus, tolerance to the semi-allogenic fetus must be supported while the mother and fetus still must be protected against infectious agents. Pregnancy is associated with a Th2 deviated immune system, away from a harmful Th1 associated immunity, although this may be a simplified view. Regulatory T cells (Tregs) are enriched in the uterus, but occur at normal frequency in the circulation. It has become increasingly evident that Tregs and T helper cells are not stably committed lineages but are plastic, showing close relationships between subsets. We hypothesize that an increased T cell flexibility in pregnancy can help to explain the paradox of simultaneous tolerance and strong antimicrobial responses. Our aim was to investigate whether the plasticity concept is applicable for the Treg subset, and if it involves the entire T helper population. Material and methods: Isolated Tregs (CD4dimCD25high) and control cells (CD4+CD25−) from second trimester pregnant (n = 14) and non-pregnant women (n = 14) were stimulated for 24 h with plate-bound anti-CD3/anti-CD28. Signature gene and protein expression of each T cell subset was measured using transcription factor expression by real time-PCR and multiplex bead array of cell culture supernatants, respectively. The whole PBMC fraction is also used in ongoing experiments and either stimulated with plate-bound anti-CD3/anti-CD28 or with the Th1, Th2 and Th17 deviating microbial agents PPD (Th1), TT (Th2) and C. albicans hyphae (Th17). After culturing, the cells are stained for intracellular transcription factors associated with Th1, Th2, Th17 and Treg immunity. Results: Stimulated Tregs from pregnant compared to non-pregnant women showed significantly higher levels of markers for Treg cells (Foxp3 mRNA), Th2 cells (GATA-3 mRNA and IL4 protein) and a tendency to increase in markers of Th17 (RORC mRNA and IL-17 protein), whereas Th1 markers (Tbet mRNA and IFN-γ) showed no difference between pregnant and non-pregnant women. Further, ongoing studies may reveal if the entire T helper population shows a higher degree of responsiveness during pregnancy. Conclusions: Our results imply an increased plasticity of the Treg population during pregnancy, suggesting that Treg cells are able to switch to a Th2/Th17-like phenotype, depending on current demands of tolerance or infectious threats.

Nyckelord

Pregnancy

T cell plasticity

Tolerance

Infectious agents

MEDICINE

MEDICIN

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