Neonatal human autologous dendritic cells pulsed with recombinant protein antigen prime the generation of non-polarized CD4 T-cell effectors

Abstract

The functional capability of human neonatal CD4 T cells to respond to vaccine antigens is frequently described as Th2 biased, but whether this is due to defective T-cell or antigen-presenting cell (APC) function is unclear. In this study, we used purified T cells and autologous monocyte-derived dendritic cells (MDDCs) as APCs to model primary and secondary neonatal CD4 T-cell responses in vitro to BBG2Na, a recombinant protein subunit vaccine candidate against respiratory syncytial virus (RSV). Neonatal MDDCs were phenotypically and functionally comparable to adult-derived MDDCs in terms of stimulatory capacity, longevity and ability to direct Th1 differentiation. When pulsed with BBG2Na, they induced antigen-specific neonatal CD4 T-cell proliferation. Analysis of cytokine production by quantitative real-time PCR showed significant production of IFN-gamma and IL-13 mRNA, analogous to the non-polarized primary cytokine mRNA response exhibited by both neonatal and adult naive CD4 T cells when primed by keyhole limpet haemocyanin. This contrasts with BBG2Na-activated adult CD45R0+ve memory CD4 T-cell responses, originally primed by natural RSV infection, which demonstrated a polarized Th1 cytokine profile. Importantly, on secondary stimulation, BBG2Na-primed neonatal CD4 T cells exhibited a 4-fold increase in antigen-specific proliferation and a 5-fold increase in IFN-gamma production. These data suggest that early life human CD4 T cells in vitro are intrinsically functionally capable of being primed by subunit vaccine candidate antigens such as BBG2Na, and differentiate into non-polarized rather than Th2 effectors.