In vivo polysaccharide-specific IgG isotype responses to intact Streptococcus pneumoniae are T cell dependent and require CD40-and B7-ligand interactions
Zq. Wu et al., In vivo polysaccharide-specific IgG isotype responses to intact Streptococcus pneumoniae are T cell dependent and require CD40-and B7-ligand interactions, J IMMUNOL, 163(2), 1999, pp. 659-667
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.