COVID-19 vaccination influences subtypes of γδ-T cells during pregnancy

Up to now, there has been insufficient clinical data to support the safety and effects of vaccination on pregnancy post COVID-19 vaccination. The γδ-T cells are considered an important component in the immune system to fight against viral infection and exhibit critical roles throughout the pregnancy period. However, the immunological roles of γδ-T cells in pregnant women with the COVID-19 vaccination remain unclear. Therefore, the objective of this study is to investigate the alteration of frequency and expression pattern of activation receptors and inhibitory receptors in γδ-T cell and its subsets in peripheral blood samples collected from non-pregnant vaccinated women, vaccinated pregnant women, and unvaccinated pregnant women. Our findings indicated that the frequency of CD3⁺γδ-T⁺ cells is lower in vaccinated pregnant women than in unvaccinated pregnant women. But no significant difference was found in the frequency of CD3⁺γδ-T⁺ cells between non-pregnant vaccinated women and vaccinated pregnant women. In addition, there were no significant differences in the frequencies of CD3⁺γδ-T⁺Vδ1⁺T cells, CD3⁺γδ-T⁺Vδ2⁺T cells, CD3⁺γδ-T⁺Vδ1^-Vδ2^-T cells, and Vδ1⁺T cell/Vδ2⁺T cell ratio between the pregnant women with or without COVID-19 vaccination. Similar results were found after comparing non-pregnant and pregnant women who received the COVID-19 vaccine. However, there was a significant difference in the fraction of Vδ1^-Vδ2^-T cells in CD3⁺γδ-T⁺ cells between non-pregnant vaccinated women and vaccinated pregnant women. The frequency of NKG2D⁺ cells in Vδ2⁺T cells was not significantly different in the vaccinated pregnant women when compared to that in unvaccinated pregnant women or non-pregnant vaccinated women. But the percentage of NKG2D⁺ cells in Vδ1⁺T cells was the lowest in pregnant women after COVID-19 vaccination. Furthermore, down-regulation of NKP46 and NKP30 were found in Vδ2⁺T and Vδ1⁺T cells in the vaccinated pregnant women, respectively. After the vaccination, up-regulation of PD-1 expression in Vδ1⁺T cells and Vδ2⁺T cells indicated γδ-T cells could respond to COVID-19 vaccination and display an exhausted phenotype following activation. In conclusion, COVID-19 vaccination influences subtypes of γδ-T cells during pregnancy, but the side effects might be limited. The phenotypical changes of Vδ1⁺T cells and Vδ2⁺T cells will be a promising predictor for evaluating the clinical outcome of the COVID-19 vaccine.