Factors influencing maternal microchimerism throughout infancy and its impact on infant T cell immunity

Abstract

Determinants of the acqusition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors which influence MMc detection and level across infancy and the effect of MMc on T cell responses to BCG vaccination in a cohort of HIV exposed, uninfected and HIV unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day one and 7, 15, and 36 weeks of life. Infants received BCG at birth, and select whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional CD4+ T cell responses. MMc was present in most infants across infancy at levels ranging from 1-1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, exclusive breastfeeding, and female sex, emphasizing that both maternal and infant factors may shape the maternal graft. Initiation of maternal antiretroviral therapy prior to pregnancy was associated with partial restoration of MMc in HIV exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional CD4+ T cell response to BCG, suggesting that MMc may functionally impact infant immunity.

Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination

“…In mice, breastmilk-derived helminth-specific T cells were protective in the offspring upon challenge with the same helminth (17), and in lambs, breastmilk-derived tetanus-specific T cells enhanced the response to tetanus vaccination in the offspring (20). Human breastmilk maternal microchimerism has not been conclusively demonstrated, although we recently found in a cohort of infants that maternal microchimerism increased up to three months of age and was positively correlated with breastfeeding (21). These data emphasize the potential for breastmilk-derived maternal T cells to become resident in the infant and provide passive protection.…”