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Departments of
*
Pathology,
Medicine,
Pediatrics, and
§
Microbiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; and
¶
Department of Microbiology, University of Alabama, Birmingham, AL 35294
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-
ß+ 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.
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Z.-Q. Wu, A. Q. Khan, Y. Shen, J. Schartman, R. Peach, A. Lees, J. J. Mond, W. C. Gause, and C. M. Snapper B7 Requirements for Primary and Secondary Protein- and Polysaccharide-Specific Ig Isotype Responses to Streptococcus pneumoniae J. Immunol., December 15, 2000; 165(12): 6840 - 6848. [Abstract] [Full Text] [PDF]
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Y.-i. Hwang, M. H. Nahm, D. E. Briles, D. Thomas, and J. M. Purkerson Acquired, but Not Innate, Immune Responses to Streptococcus pneumoniae Are Compromised by Neutralization of CD40L Infect. Immun., February 1, 2000; 68(2): 511 - 517. [Abstract] [Full Text] [PDF]
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Y. Xu, M. Ma, G. C. Ippolito, H. W. Schroeder Jr., M. C. Carroll, and J. E. Volanakis Complement activation in factor D-deficient mice PNAS, December 4, 2001; 98(25): 14577 - 14582. [Abstract] [Full Text] [PDF]
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