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J Leukoc Biol ; 78(5): 1060-9, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16081596

ABSTRACT

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.


Subject(s)
Antibodies, Blocking/pharmacology , Antigens, Differentiation/immunology , Pneumococcal Infections/immunology , Pneumococcal Vaccines/pharmacology , Polysaccharides, Bacterial/immunology , Adoptive Transfer , Animals , Antibodies, Blocking/immunology , Antigens, CD , Antigens, Differentiation/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/transplantation , CTLA-4 Antigen , Cytokines/genetics , Cytokines/immunology , Dose-Response Relationship, Drug , Immunization , Mice , Mice, Inbred BALB C , Mice, Nude , Mice, SCID , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/immunology , Polysaccharides, Bacterial/drug effects , RNA, Messenger/genetics , RNA, Messenger/immunology , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/immunology , Survival Rate , T-Lymphocytes/immunology , T-Lymphocytes/transplantation
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