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* Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; and
Division of Infectious Disease, Case Western Reserve University, Cleveland, OH 44106
Macrophages are less effective than DC at priming naive CD4+ T cells, suggesting that DC are unique in initiating T cell-dependent Ab responses. We compared the ability of DC and macrophages, pulsed in vitro with Streptococcus pneumoniae, to elicit protein- and polysaccharide-specific Ig isotype production upon adoptive transfer into naive mice. S. pneumoniae-activated DC secreted more proinflammatory and anti-inflammatory cytokines, expressed higher levels of surface MHC class II and CD40, and presented S. pneumoniae or recombinant pneumococcal surface protein A (PspA) to a PspA-specific T hybridoma more efficiently than macrophages. However, upon adoptive transfer into naive mice, S. pneumoniae-pulsed macrophages elicited an IgM or IgG anti-PspA and anti-polysaccharide response comparable in serum titers and IgG isotype distribution to that induced by DC. The IgG anti-PspA response, in contrast to the IgG anti-polysaccharide, to S. pneumoniae-pulsed macrophages was T cell-dependent. S. pneumoniae-pulsed macrophages that were paraformaldehyde-fixed before transfer or lacking expression of MHC class II or CD40 were highly defective in eliciting an anti-PspA response, although the anti-polysaccharide response was largely unaffected. To our knowledge, these data are the first to indicate that macrophages can play an active role in the induction of a T cell-dependent humoral immune response in a naive host.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant 2R01 AI49192 from the National Institutes of Health and the Uniformed Services University of the Health Sciences Dean’s Research and Education Endowment Fund.
Opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences.
2 Address correspondence and reprint requests to Dr. Clifford M. Snapper, Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814. E-mail address: csnapper{at}usuhs.mil
3 Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; Pn14, intact Streptococcus pneumoniae capsular type 14; PspA, pneumococcal surface protein A; PPS14, capsular polysaccharide, serotype 14; BMM, bone marrow-derived macrophage; PerM, peritoneal macrophage; BMDC, bone marrow-derived DC; TNP, trinitrophenyl; WT, wild type.
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  J. Colino, G. Chattopadhyay, G. Sen, Q. Chen, A. Lees, D. H. Canaday, A. Rubtsov, R. Torres, and C. M. Snapper Parameters Underlying Distinct T Cell-Dependent Polysaccharide-Specific IgG Responses to an Intact Gram-Positive Bacterium versus a Soluble Conjugate Vaccine J. Immunol., August 1, 2009; 183(3): 1551 - 1559. [Abstract] [Full Text] [PDF]
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