Inherited maternal memory T cells protect offspring from respiratory viral infection through disease tolerance

Abstract

Maternal immune transfer is a powerful mechanism for early-life protection from infection, yet the full repertoire of protective factors remains unknown. We discovered that maternal memory T cells are both necessary and sufficient to protect offspring from lethal respiratory infection. This antigen-specific protection operated independently of maternal antibodies and offspring T cell responses and required IL-10 produced by maternal T cells. Transfer of protective maternal T cells reduced offspring inflammatory responses and lung tissue damage without affecting viral burdens, indicating that maternal memory T cells directly suppress pathogenic innate inflammatory responses to preserve offspring health. Critically, maternal vaccination similarly protected offspring in a T cell-dependent manner. These findings reveal maternal antigen-specific T cell transfer as a complementary immunological defense mechanism to protect offspring against pathogens that escape maternal antibodies, with broad implications for maternal vaccination strategies.