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 cell independent and do not require CD40 ligand (CD40L). However, little is known regarding the regulation of in vivo PS-specific Ig responses to intact bacteria. We immunized mice with a nonencapsulated, type 2 Streptococcus pneumoniae (R36A) and compared the parameters that regulated in vivo Ig isotype responses to the bacterial cell wall C-PS determinant, phosphorylcholine (PC), relative to Ig responses to the cell wall protein, pneumococcal surface protein A. Consistent with previous reports using soluble PS and protein Ags, the anti-PC and anti-pneumococcal surface protein A responses differed in that the anti-PC response was induced more rapidly, had a distinctive Ig isotype profile, and failed to demonstrate boosting upon secondary challenge with R36A. However, in contrast to previous studies, the IgG anti-PC response was TCR-alphabeta+ T cell dependent, required CD40L, and was blocked by administration of CTLA4 Ig. The nature of the T cell help for the anti-PC response had distinct features in that it was only partially blocked by CTLA4 Ig and was dependent upon both CD4+ and CD8+ T cells. Surprisingly, whereas the IgM anti-PC response was largely T cell independent, a strong requirement for CD40L was still observed, suggesting the possibility of an in vivo T cell-independent source for CD40L-dependent help. These data suggest that the regulatory parameters that govern in vivo Ig responses to purified, soluble PS Ags may not adequately account for PS-specific Ig responses to intact bacteria.
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 2081, USA.
Z Q
ZQ
Wu
Q
Q
Vos
Y
Y
Shen
A
A
Lees
S R
SR
Wilson
D E
DE
Briles
W C
WC
Gause
J J
JJ
Mond
C M
CM
Snapper
D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D008024:Ligands; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors
D018122:B7-1 Antigen; D001426:Bacterial Proteins; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D008024:Ligands; D008562:Membrane Glycoproteins; D011135:Polysaccharides, Bacterial; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C051592:pneumococcal surface protein A; D010767:Phosphorylcholine; D023201:CD40 Ligand