Summary: Infections with intracellular pathogens are often more severe or more prolonged in young infants suggesting that T cell-mediated immune responses are different in early life. Whereas neonatal immune responses have been quite extensively studied in murine models, studies of T cell-mediated immunity in human newborns and infants are scarce. Qualitative and quantitative differences when compared with adult immune responses have been observed but on the other hand mature responses to certain vaccines and infectious pathogens were demonstrated during the postnatal period and even during foetal life. Herein, we review the evidence suggesting that under appropriate conditions of stimulation, protective T cell-mediated immune responses could be induced by vaccines in early life.

Neonates are particularly susceptible to infection. This vulnerability occurs despite their responsiveness to most vaccines. However, current vaccines do not target the pathogens responsible for most of the severe neonatal infections, and the time it takes to induce protective pathogen-specific immunity after vaccination limits protection in the first days to weeks of life. Alternative strategies include using vaccines to broadly stimulate neonatal immunity in a pathogen-agnostic fashion or vaccinating women during pregnancy to induce protective antibodies that are vertically transferred to offspring within their window of vulnerability. Protection may be further improved by integrating these approaches, namely vaccinating the neonate under the cover of vertically transferred maternal immunity. The rationale for and knowledge gaps related to each of these alternatives are discussed.

Cytotoxic CD4 (CD4_CTX) T cells are emerging as an important component of antiviral and antitumor immunity, but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant proportion of CD4 T cells displays cytotoxic functions. We observed that the transcriptional program of these cells was enriched in CD8 T cell lineage genes despite the absence of ThPOK downregulation. We further show that establishment of CD4_CTX-specific transcriptional and epigenetic programs occurred in a stepwise fashion along the Th1-differentiation pathway. In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK. This work elucidates the molecular program of human CD4_CTX T cells and identifies potential targets for immunotherapy against viral infections and cancer.

BackgroundCytomegalovirus (CMV) is the most common congenital infection and can follow primary and recurrent maternal infection. We studied correlate