CCR5/CCR6 Chemokine Receptor Profiles Differ in γδTCR Intensity-Defined Subsets but Remain Conserved Across Conventional and NK-like γδT Cells During Healthy First-Trimester Pregnancy

During pregnancy, immune tolerance toward the semi-allogeneic fetus must be established. γδT cells constitute a distinct T-cell lineage characterized by expression of the γδT-cell receptor (γδTCR). They combine rapid innate-like responses with adaptive immune functions and contribute to feto-maternal immune regulation; however, their peripheral phenotypic characteristics, including chemokine receptor (ChR) profiles potentially relevant to decidual recruitment, remain incompletely characterized. Peripheral blood from healthy non-pregnant and first-trimester pregnant women was analyzed by flow cytometry to assess γδT-cell phenotypes and CCR5/CCR6 ChR expression. Analysis of γδT-cell subsets defined by lower (γδTCRdim) or higher (γδTCRbright) surface γδTCR expression showed that CCR5−/CCR6− cells were more frequent in γδTCRbright cells, whereas CCR5+ phenotypes were more prominent in γδTCRdim cells; CD4/CD8 and CD56/CD8 distributions were comparable. Resting γδT cells were mainly CD4−/CD8−, whereas recently activated CD69+ γδT cells had increased CD4+ or CD8+ single-positive frequencies. Compared with non-γδT cells, γδT cells showed distinct CD4/CD8-linked CCR5/CCR6 organization, including a CCR5+/CCR6− preference. Unlike non-γδT cells, conventional CD56− and NK-like CD56+ γδT cells retained similar CCR5/CCR6 profiles across CD4/CD8-defined subsets. PMA/ionomycin-stimulated samples generally exhibited lower CCR5+ and higher CCR5− frequencies across CD4− conventional and NK-like γδT cell subsets. Pregnancy-related circulating γδT-cell phenotype changes were negligible, possibly reflecting decidual immune adaptation. Overall, the study highlights γδTCR intensity-linked ChR heterogeneity and, in contrast to non-γδT cells, conserved CCR5/CCR6 organization across CD56-defined γδT-cell subsets. Broader ChR phenotyping and functional migration analyses could clarify the biological relevance of these subset-specific differences.