Blockade of CTLA-4 (CD152) enhances the murine antibody response to pneumococcal capsular polysaccharides.
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.
Boudewijns
Michaël
M
Experimental Laboratory Medicine, Department of Molecular Cell Biology, Faculty of Medicine, Catholic University Leuven, Belgium.
Jeurissen
Axel
A
Wuyts
Margaretha
M
Moens
Leen
L
Boon
Louis
L
Van Neerven
Joost J
JJ
Kasran
Ahmad
A
Overbergh
Lut
L
Lenaerts
Caroline
C
Waer
Marc
M
Mathieu
Chantal
C
Ceuppens
Jan L
JL
Bossuyt
Xavier
X
D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation
D019138:Antibodies, Blocking; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D012333:RNA, Messenger