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Published online before print June 5, 2007

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(Journal of Leukocyte Biology. 2007;82:638-644.)
© 2007 by Society for Leukocyte Biology

Distinct approaches to investigate the importance of the murine 4-1BB–4-1BBL interaction in the antibody response to Streptococcus pneumoniae

Leen Moens^*, Axel Jeurissen^*, Robert S. Mittler, Greet Wuyts^*, George Michiels^*, Louis Boon, Jan L. Ceuppens and Xavier Bossuyt^*,1

^* Laboratory of Experimental Laboratory Medicine, Department of Molecular Cell Biology, and
Laboratory of Experimental Immunology, Department of Pathophysiology, Faculty of Medicine, Catholic University Leuven, Leuven, Belgium;
Department of Surgery and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA; and
Bioceros, Utrecht, The Netherlands

¹ Correspondence: Laboratory of Experimental Laboratory Medicine, Department of Molecular Cell Biology, Faculty of Medicine, Catholic University Leuven, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. E-mail: xavier.bossuyt{at}uz.kuleuven.ac.be

Protection against infection with Streptococcus pneumoniae is based mainly on the generation of antibodies to the pneumococcal capsular polysaccharides (caps-PS). Although caps-PS are considered thymus-independent antigens, there is a growing body of evidence that T lymphocytes and costimulatory molecules are involved in the regulation of the antibody response to caps-PS. We investigated whether the interaction between 4-1BB and 4-1BB ligand (4-1BBL) is involved in the modulation of the antibody response to caps-PS after immunization with Pneumovax® or with intact heat-killed S. pneumoniae. Treatment with agonistic anti-4-1BB mAb, which mimics engagement of 4-1BB by 4-1BBL, had no effect on the IgG and IgM immune response to caps-PS (Serotype 3) after immunization with Pneumovax or with S. pneumoniae Serotype 3. However, anti-4-1BB treatment strongly inhibited the IgG response to pneumococcal surface protein A (PspA). By contrast, the IgG anti-caps-PS (Serotype 3) antibody response was reduced strongly in 4-1BBL^–/– mice immunized with S. pneumoniae Serotype 3. The IgG anti-PspA antibody response in the 4-1BB^–/– mice was comparable with the immune response in the wild-type mice. We conclude that distinct pathways are involved in the humoral antibody response to pneumococcal antigens, depending on the nature of the antigen and the context in which the different antigens are presented. The 4-1BB–4-1BBL interaction is not involved in the antibody response to soluble caps-PS. The influence of the 4-1BB–4-1BBL interaction in the immune reaction to S. pneumoniae Serotype 3 depends on the experimental system used.

Key Words: capsular polysaccharides • pneumococcal surface protein A • costimulatory molecule

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