NIH Research Festival
We hypothesized that CD4+ T cell-dependent polysaccharide (PS)- and protein-specific IgG responses to intact bacteria versus soluble PS-protein conjugates involve utilization of distinct APC. Confocal microscopy demonstrated that intact Streptococcus pneumoniae (Pn) co-localized within splenic mouse monocytic CD11b+CD11c- cells following i.p. immunization, whereas a pneumococcal conjugate vaccine co-localized within splenic CD11c+ cells. To explore the functional implications of this dichotomy we used clodronate liposomes (CL), to selectively deplete phagocytic cells, including macrophages, monocytic CD11b+ cells, marginal zone macrophages and marginal metallophilic macrophages but not conventional Dendritic cells (cDCs). CL injection prior to i.p. immunization with OVA peptide-expressing Pn resulted in marked inhibition of OVA-specific CD4+ T cell proliferation, whereas it had no effect on OVA-specific CD4+ T cell proliferation in response to an OVA-polysaccharide conjugate or OVA protein alone. Of interest, CL markedly reduced primary and secondary protein-specific IgG responses to Pn, as well as conjugate vaccine or protein alone. CL only modestly reduced PS-specific IgG responses to intact Pn and conjugate vaccine. These data suggest that CL-sensitive cells critically mediate early CD4+ T cell proliferation in response to an intact bacterium, but that they are also required for downstream events in response to a soluble antigen.
Scientific Focus Area: Immunology
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