In vivo polysaccharide-specific IgG isotype responses to intact Streptococcus pneumoniae are T cell dependent and require CD40-and B7-ligand interactions

In vivo Ig responses to soluble, haptenated polysaccharide (PS) Ags are T c ell independent and do not require CD40 ligand (CD40L). However, little is known regarding the regulation of in vivo PS-specific Ig responses to intac t bacteria. We immunized mite with a nonencapsulated, type 2 Streptococcus pneumoniae (R36A) and compared the parameters that regulated in vivo Ig iso type responses to the bacterial cell wall C-PS determinant, phosphorylcholi ne (PC), relative to Ig responses to the cell wall protein, pneumococcal su rface protein A. Consistent with previous reports using soluble PS and prot ein Ags, the anti-PC and anti-pneumococcal surface protein A responses diff ered in that the anti-PC response was induced more rapidly, had a distincti ve Ig isotype profile, and failed to demonstrate boosting upon secondary ch allenge,vith R36A, However, in contrast to previous studies, the IgG anti-P C response was TCR-alpha beta(+) T cell dependent, required CD40L, and was blocked by administration of CTLA4 Ig, The nature of the T cell help for th e anti-PC response had distinct features in that it was only partially bloc ked by CTLA4 Ig and was dependent upon both CD4(+) and CD8(+) T cells. Surp risingly, whereas the IgM anti-PC response was largely T cell independent, a strong requirement for CD40L was still observed, suggesting the possibili ty of an in vivo T cell-independent source for CD40L-dependent help. These data suggest that the regulatory parameters that govern in vivo Ig response s to purified, soluble PS Ags may not adequately account for PS-specific Ig responses to intact bacteria.