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Originally published online as doi:10.1189/jlb.1004562 on August 4, 2005

Published online before print August 4, 2005
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(Journal of Leukocyte Biology. 2005;78:1060-1069.)
© 2005 by Society for Leukocyte Biology

Blockade of CTLA-4 (CD152) enhances the murine antibody response to pneumococcal capsular polysaccharides

Michaël Boudewijns*, Axel Jeurissen*, Margaretha Wuyts*, Leen Moens*, Louis Boon{dagger}, Joost J. Van Neerven{dagger}, Ahmad Kasran{ddagger}, Lut Overbergh§, Caroline Lenaerts, Marc Waer, Chantal Mathieu§, Jan L. Ceuppens{ddagger} and Xavier Bossuyt*,1

* Experimental Laboratory Medicine, Department of Molecular Cell Biology, and Laboratories of
{ddagger} Experimental Immunology, Department of Pathophysiology,
§ Experimental Medicine and Endocrinology (LEGENDO), and
Experimental Transplantation, Faculty of Medicine, Catholic University Leuven, Belgium; and
{dagger} Bioceros, B.V., Amsterdam, The Netherlands

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

The capsular polysaccharides (caps-PS) of Streptococcus pneumoniae are classified as thymus-independent antigens. Nevertheless, T lymphocytes can modulate the antibody response to caps-PS. In this study, we show that anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) treatment, along with administration of caps-PS to BALB/c mice, resulted in a dose-dependent generation of a strong caps-PS-specific antibody response. Anti-CTLA-4 treatment had no effect on the immunoglobulin G (IgG) antibody production in athymic nu/nu mice. Anti-CTLA-4 treatment stimulated the IgG antibody production in severe combined immunodeficiency (SCID)/SCID mice reconstituted with CTLA-4–/– B lymphocytes and wild-type T lymphocytes. This excluded the possibility that anti-CTLA-4 enhanced antibody production by direct interaction with B lymphocytes. Anti-CTLA-4 treatment enhanced the antibody production in SCID/SCID mice reconstituted with B lymphocytes and CD4(+) and CD8(+) T lymphocytes but not in SCID/SCID mice reconstituted with B lymphocytes in the absence of CD4(+) and/or CD8(+) cells. Administration of anti-CTLA-4 in BALB/c mice but not in nu/nu mice resulted in a markedly increased production of interleukin (IL)-2, IL-4, and interferon-{gamma}. Taken together, these data strongly suggest a role of T lymphocytes and CTLA-4 in the regulation of the antibody response to caps-PS.

Key Words: Streptococcus pneumoniae • T lymphocytes




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