T-cell modulation of the antibody response to bacterial polysaccharide antigens

Abstract

Pretreatment of mice with subimmunogenic doses of meningococcal polysaccharide (MP), Pseudomonas aeruginosa lipopolysaccharide (PA), or Streptococcus mutans polysaccharide (SM) resulted in suppression of antibody response. The transfer of putative suppressor T cells (T. cells) from donor mice primed with a subimmunogenic dose of MP to naive recipients at the time of immunization with MP substantially reduced the magnitude of the antibody response. Also, the infusion of B cells taken from animals immunized with either MP or PA suppressed the antibody response of naive recipients to MP or PA, respectively, relative to controls, suggesting that T. cells respond to determinants on immune B cells. We observed that the injection of concanavalin A or phytohemagglutinin (two lectins known to augment the activity of amplifier T cells [Ta cells]) 2 days postimmunization enhanced the antibody response to MP and SM. In addition, Ta-cell activity was transferred to naive animals by using spleen cells. Although the administration of phytohemagglutinin at the time of immunization with MP also resulted in increased antibody response, the injection of concanavalin A simultaneous with immunization resulted in a suppression of the antibody response to MP. Although Ts cells generated in response to pneumococcal polysaccharide type III were found to respond to monoclonal antibody Ly-m22, Ta cells responded to monoclonal antibodies L3T4 and Ia but not to Ly-m22. These studies suggest that Ta and Ts cells can modulate the antibody response to MP, SM, and PA in a positive and negative manner, respectively.

Regulation of magnitude of antibody response to bacterial polysaccharide antigens by thymus-derived lymphocytes

“…MPL acts mainly to inactivate Ts function, whereas, in the absence of Ts activity, TDM appears to increase the extent to which B cells proliferate in response to antigen. In view of these findings and those of other studies (35,36), the combination of TDM and MPL should be a powerful adjuvant with special application to poorly immunogenic polysaccharide antigens (e.g., Haemophilus influenzae type b polysaccharide and Neisseria meningitidis group A and C polysaccharides) in the young.…”

“…The magnitude of the antibody response to the capsular polysaccharide of type III Streptococcus pneumoniae (SSS-III) is regulated in a positive and negative manner by thymus-derived (T) lymphocytes (1,10); however, only recently have such control mechanisms been implicated in the antibody response to other bacterial polysaccharide antigens, e.g., Neisseria meningitides group A and C capsular polysaccharides (29,35), Pseudomonas aeruginosa lipopolysaccharide (LPS) (31,35), Streptococcus mutans polysaccharide (4), Serratia marcescens LPS (16,17), and Escherichia coli 055 LPS (16,17). This suggests that T-cell regulation may be a general feature of these as well as other antibody responses.…”

Immunogenicity of meningococcal polysaccharide ACWY vaccine in primary immunized or revaccinated adults

“…Pre-existing antibody may interfere with Ps vaccination through different mechanisms, including the reduced availability of Ps antigens for epitope masking or competition with the B cell receptor and/or the possible formation of Ps antigen-antibody complexes with consequent antigen clearance or transduction of FcRmediated negative signals which, in turn, would influence the B cell function negatively in a feedback control of new antibody secretion [38]. Furthermore, from the 1980s belief in the absolute T cell-independence of Ps antigens has been questioned [39][40][41], and even more recently [42] also taking advantage of the systems biological approach [43]. Our data favour the possibility that high prevaccination antibody levels may have a prevalent role over the B cell clone exhaustion as a cause for the reduced increase of anti-Men-PsC and PsW 135 IgG, in addition to age, which may be responsible for hyporesponsiveness to PsW 135 and PsY, as already observed with influenza vaccination [44].…”

Dynamics of the Murine Humoral Immune Response toNeisseria meningitidisGroup B Capsular Polysaccharide

“…In any event, the poor immunogenicity of CpsB is associated with the ␣(238) linkage. Purified CpsC, a homopolymer of ␣(239)-linked sialic acid, has been shown to be immunogenic in mice (48).…”