The CD4+ T cell‐ and SAP‐dependent IgG anti‐polysaccharide response to intact Streptococcus pneumoniae, in contrast to pneumococcal conjugate vaccine, is ICOS‐independent

The IgG murine anti‐polysaccharide (PS) and anti‐protein responses to intact Streptococcus pneumoniae (Pn) are CD4+ T cell and B7/CD28 dependent. However, in contrast to the IgG anti‐protein response, the primary IgG anti‐PS response peaks more rapidly, fails to generate memory, and requires a shorter period of CD4+ T cell help and B7‐dependenrt costimulation. Although CD28 is constitutively expressed on naïve CD4+ T cells, ICOS is typically induced during the first 48h following immunization. We now show that ICOS−/− mice immunized with intact Pn elicit a normal IgM and IgG anti‐PS response but a completely defective anti‐protein response, relative to WT mice. Neutralizing anti‐ICOS‐ligand mAb injected at the time of primary, but not secondary, Pn immunization was inhibitory for the anti‐protein response. In distinct contrast, ICOS−/− mice injected with a pneumococcal conjugate vaccine, exhibited both a defective IgG anti‐PS, as well as IgG anti‐protein response. Although the adaptor molecule, SAP is thought to play a key role in T cell‐dependent humoral immune responses through induction of ICOS on CD4+ T cells, SAP−/− mice challenged with intact Pn were highly defective in eliciting the ICOS‐independent IgG anti‐PS response. These data are the first to demonstrate a CD4+ T cell and SAP‐dependent humoral immune response that is ICOS‐independent. Supported by NIH grant 2R01 AI49192