Distinct Cellular Pathways for Induction of CD4+ T Cell–Dependent Antibody Responses to Antigen Expressed by Intact Bacteria Versus Isolated Soluble Antigen

Abstract

Uptake of intact bacteria and soluble Ags by APCs is mediated by phagocytosis and endocytosis or pinocytosis, respectively. Thus, we predicted that injection of clodronate-containing liposomes (CLs), which selectively deplete cells efficient in phagocytosis, would inhibit murine CD4+ T cell–dependent IgG responses to Ags expressed by intact bacteria but not isolated soluble Ags. Surprisingly, injection of CLs markedly inhibited protein-specific IgG responses to intact, heat-killed Streptococcus pneumoniae, as well as a soluble OVA-polysaccharide conjugate or OVA alone. IgG anti-polysaccharide responses to bacteria and conjugate were also reduced, but more modestly. In both instances, CL-mediated inhibition was associated with a significant reduction in induced germinal centers and CD4+ germinal center T follicular helper cells. However, CL injection, which largely abrogated the proliferative response of adoptively transferred OVA peptide-specific–transgenic CD4+ T cells in response to immunization with S. pneumoniae expressing OVA peptide, did not inhibit T cell proliferation in response to OVA–polysaccharide conjugate or OVA. In this regard, monocyte-derived cells, depleted by CLs, internalized S. pneumoniae in vivo, whereas CD11clow dendritic cells, unaffected by CL injection, internalized soluble OVA. Ex vivo isolation and coculture of these respective APCs from S. pneumoniae- or OVA-immunized mice with OVA-specific T cells, in the absence of exogenous Ag, demonstrated their selective ability to induce T cell activation. These data suggest that, although distinct APCs initiate CD4+ T cell activation in response to Ag expressed by intact bacteria versus Ag in soluble form, CL-sensitive cells appear to be necessary for the subsequent IgG responses to both forms of Ag.

Pneumococcal Polysaccharide Vaccine Ameliorates Murine Lupus

“…Previous studies indicate that polysaccharide vaccines may generate T FH cell responses in mice and humans, with a link to a functional association with the immunogenicity of the vaccine (50, 51). However, data on the effect of Prevnar-13 on T FH and T FR (a subset of regulatory T cells that controls T FH activation) are missing.…”

Carbomer-based Nano-Emulsion Adjuvant Enhances Dendritic Cell Cross-presentation via Lipid Body Formation Independent of Glycolysis

“…BMDCs were incubated with pre-warmed AF-647 OVA with or without 1% ADJ for 10 or 30 minutes. The pH of OVAcontaining endosomal compartment was determined using ovalbumin-conjugated with pHAB Amine Reactive dye as previously described with some modifications (Kar et al, 2016, Nath et al, 2016. Conjugation of ovalbumin with pHAB-amine reactive dye was performed according to manufacturer's instructions.…”

Distinct Immunologic Properties of Soluble Versus Particulate Antigens

“…Splenic macrophages and monocytes (and monocyte-derived cells), but not conventional DCs or neutrophils, were depleted by i.v. injection of CL ( 76 ). Surprisingly, injection of CL markedly inhibited protein-specific IgG responses to a soluble PS–OVA conjugate or OVA alone, as well as to intact, inactivated S. pneumoniae .…”

“…These data provided strong support to the notion that distinct APCs initiate CD4 + T cell activation in response to antigen expressed by intact bacteria versus antigen in soluble form. However, CL-sensitive cells appear necessary for the subsequent IgG responses to both forms of antigen ( 76 ).…”