Neonatal human autologous dendritic cells pulsed with recombinant protein antigen prime the generation of non-polarized CD4 T-cell effectors.
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.
Matthews
Nick C
NC
Children's Research Centre, Our Lady's Hospital for Sick Children, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Crumlin, Dublin 12, Ireland.
Power
Ultan F
UF
Reen
Denis J
DJ
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D011994:Recombinant Proteins / Q000276:immunology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; C472186:BBG2Na vaccine; D006684:HLA-DR Antigens; D018793:Interleukin-13; D007376:Interleukin-2; D015848:Interleukin-5; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D022261:Respiratory Syncytial Virus Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin