T Cell-Independent Antigens Type 2

Mond, James J.; Lees, Andrew; Snapper, Clifford M.

doi:10.1146/annurev.iy.13.040195.003255

Cited by 756 publications

(635 citation statements)

References 53 publications

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“…For example, the role of T lymphocytes in the immune response to caps-PS remains a matter of debate. Being TI-2 antigens, caps-PS stimulate antibody production in the absence of MHC class II-restricted T lymphocyte help [19]. We confirmed the non-cognate nature of the anti-caps-PS immune response by demonstrating that blocking MHC class II mAb did not inhibit the antibody response to caps-PS.…”

Section: Discussionsupporting

confidence: 62%

The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40‐CD40 ligand interaction

et al. 2004

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Protection against infections with Streptococcus pneumoniae is mediated by antibodies against the capsular polysaccharides (caps-PS). Here we show that in in vitro experiments CD4 + T lymphocytes stimulate and CD8 + T lymphocytes inhibit the human anti-caps-PS antibody response. Using antagonistic anti-CD40 and antagonistic anti-CD40 ligand (CD40L) monoclonal antibodies, we showed that the CD4 + T lymphocyte-mediated stimulation is dependent on the CD40-CD40L interaction. The role of CD40L was further illustrated by the observation that CD4 + T lymphocytes obtained from a patient with hyper-IgM syndrome were unable to enhance the immune response to caps-PS. Furthermore, CD4 + T lymphocytes from cord blood, which did not express CD40L in response to stimulation with caps-PS, failed to stimulate the antibody response of adult B lymphocytes to caps-PS. These in vitro findings were confirmed by in vivo experiments in which SCID/SCID mice were reconstituted with human mononuclear cells. Furthermore, we showed that caps-PS induce production of IL-4, IL-6, IL-10, and IFN-+ , and that this enhanced production was inhibited by blocking the CD40-CD40L interaction. This is the first demonstration that the human immune response to caps-PS, which is markedly regulated by T lymphocytes, is dependent on the CD40-CD40L interaction.

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Section: Discussionsupporting

confidence: 62%

The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40‐CD40 ligand interaction

et al. 2004

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“…The molecular mechanisms by which TI-2 immunogens with repeating structures, such as bacterial polysaccharides, stimulate an antibody response have been revealed by the work of Snapper and coworkers (Mond et al 1995, Snapper and Mond 1996, Snapper et al 1997. In brief, the polysaccharide crosslinks approximately 15-20 surface immunoglobulin molecules (sIg) molecules present on a B cell of appropriate specificity, leading through a series of intermediate protein phosphorylation steps to an increase in free intracellular calcium.…”

Section: The Molecular Mechanisms Of the Generation Of Immune Responsmentioning

confidence: 99%

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Jones

2005

An. Acad. Bras. Ciênc.

168

117

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Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development.This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

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“…The pneumococcus is the major cause of otitis media illness in children [2], the most common cause of community-acquired pneumonia both among adults [3] and children [4,5], and ranks as the second most common pathogen of bacterial meningitis [6]. Infants and young children are unable to respond adequately to the pneumococcal PS (PPS), which are T cell-independent type 2 antigens [7]. The absence of T cell help in Ab responses to PS is due to their inability to associate with MHC class II molecules on APC [8,9].…”

Section: Introductionmentioning

confidence: 99%

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

et al. 2006

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Immunization with a tetanus-protein (TT) pneumococcal polysaccharide (PPS) conjugate vaccine (Pnc1-TT) induces protective immunity against lethal pneumococcal infections in neonatal and infant mice, but anti-PPS IgG response and protective efficacy is lower than in adult mice. Here, we show that reduced antibody (Ab) response and protection against infections is directly related to impaired T cell response to the carrier. Whereas spleen cells from adult mice immunized with Pnc1-TT responded with proliferation and IFN-gamma secretion to in vitro stimulation with TT, spleen cells from neonatal and infant mice did not. However, significant, but age dependent, Th2-cytokine responses were observed in mice immunized with Pnc1-TT. Impaired IFN-gamma production upon TT-stimulation in vitro was also reflected in reduced IFN-gamma/IL-5 ratio. The IL--5 response correlated with IgG anti-PPS titers, and the lack of PPS Ab in the majority of neonatal mice was clearly associated with absence of carrier-specific IL-5 production. These results show that immunization with Pnc1-TT induces carrier-specific T cell responses that increase with age and determine the levels of PPS-specific Ab elicited. Whereas a weak and Th2-biased response was observed in neonatal mice, infant mice showed a mixed Th1-Th2 response as observed in adults

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T Cell-Independent Antigens Type 2

Cited by 756 publications

References 53 publications

The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40‐CD40 ligand interaction

The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40‐CD40 ligand interaction

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

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