Effectiveness of Lipid and Lipidophilic Substances as Adjuvants

Dresser, D. W.

doi:10.1038/1911169a0

Cited by 136 publications

(60 citation statements)

References 3 publications

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“…Mice were boosted at six weeks post-priming and then, in some experiments, again ten weeks postpriming, with the same dose of antigen as used for priming but boosting antigen was administered intraperitoneally. This protocol has been shown previously to induce immunity and not tolerance [71,72].…”

Section: Antigen Priming and Boostingmentioning

confidence: 94%

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

Wang

Davies

2007

International Immunopharmacology

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Treatment with a cocktail of CD4 and CD8-specific monoclonal antibodies (mAb) induces long-term transplantation tolerance and regulatory CD4 + T cells that induce tolerance in non-tolerant T cells. In contrast, treatment with a CD4-specific mAb alone fails to induce long-term tolerance. The current study was designed to test the hypothesis that CD8 blockade plays a role in promoting the development of CD4 + regulatory T cells.Using the DO11.10 CD4 + TCR transgenic mouse model we show that treatment with a CD4/CD8-specific mAb cocktail induces antigen-specific tolerance to OVA, measured by a significant decrease in OVA-specific IgG, on challenge with antigen. Although treatment with OVA and the CD4-specific mAb alone also induces a significant decrease in OVA-specific antibody, the number of DO11.10 cells is significantly greater in mice treated with the CD4/CD8-specific mAb cocktail, and this is associated with a significant increase in proliferation of DO11.10 cells in response to specific antigen. DO11.10 cells sorted from mice made tolerant to OVA with the CD4/CD8-specific mAb cocktail promote an OVA-specific IgG1 (Th2-type) response but not an OVA-specific IgG3 (Th1-type) response on transfer into new syngeneic recipients, suggesting their ability to regulate the type of antigen-specific immune response that ensues after priming with antigen. In addition, DO11.10 cells from tolerant mice express markers that are characteristic of CD4 + regulatory cells, including FOXP3, GITR and CTLA4, but not CD25. Taken as a whole, these data suggest that CD8 blockade promotes CD4 + FOXP3 + regulatory CD4 + T cells by promoting their proliferation in tolerant mice.

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Section: Antigen Priming and Boostingmentioning

confidence: 94%

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

Wang

Davies

2007

International Immunopharmacology

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“…Recently, a correlation between the mitogenic effect of LPS on B cells and its adjuvant property has been suggested (24). The transformation of the induction of tolerance into an immunogenic stimulus could be viewed as a most stringent manifestation of this adjuvant effect (25) specifically occurring on B cells. In this light, the inability of LPS to interfere with the induction of unresponsiveness in specific T cells could be related to the inability of LPS to mitogenically stimulate such cells.…”

Section: Discussionmentioning

confidence: 99%

The Ability of Bacterial Lipopolysaccharide to Modulate the Induction of Unresponsiveness to a State of Immunity

Louis

Chiller

Weigle

1973

The Journal of Experimental Medicine

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There exists a body of evidence which details that the antibody response to a number of different antigens requires the cooperation between thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) in a reaction whose net effect is the production of specific antibody by B cells (1). Both of these lymphocyte classes can be made specifically unresponsive to a given antigen (2), although each specific population displays a distinct kinetic pattern in the induction and maintenance of unresponsiveness (3).Bacterial lipopolysaccharides (LPS) 1 are mitogenic for B lymphocytes (4, 5), a phenomenon which may be related to their ability to circumvent the requirement of T cells for antibody formation to antigens which normally require cellular cooperation. The latter has been demonstrated both in vivo or in vitro using such T celldependent antigens as sheep erythrocytes (6-8), haptens (9, 10), and serum proteins (11). LPS can also prevent immunological unresponsiveness. This effect was originally described by Claman (12), who observed that mice which were given LPS after a normally tolerogenic dose of bovine gamma globulin (BGG) did not become tolerant. Golub and Weigle (13) subsequently defined the temporal relationship between the injection of tolerogen and LPS and furthermore demonstrated that the effect of LPS on the induction of tolerance was independent of its activity on the phagocytic index of the reticuloendothelial system.

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“…Thus, these peptide-MHC complexes would be expected to be just as "foreign" to the immune system as those derived from microbes. Clues about a possible explanation for this paradox come from experiments performed by Dresser (46,47), which showed that the immunogenicity of purified antigens was determined by factors in addition to foreignness. He showed that even foreign antigens failed to induce immunity unless they were injected with an adjuvant (46).…”

Section: Developmentally Regulated Antigensmentioning

confidence: 99%

“…Clues about a possible explanation for this paradox come from experiments performed by Dresser (46,47), which showed that the immunogenicity of purified antigens was determined by factors in addition to foreignness. He showed that even foreign antigens failed to induce immunity unless they were injected with an adjuvant (46). Adjuvants are components of microbes, for example lipopolysaccharide or muramyl dipeptide, that induce inflammation (48).…”

Section: Developmentally Regulated Antigensmentioning

confidence: 99%

The anatomy of T-cell activation and tolerance.

Mondino

Khoruts²,

Jenkins³

1996

Proc. Natl. Acad. Sci. U.S.A.

206

106

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The mammalian immune system must specifically recognize and eliminate foreign invaders but refrain from damaging the host. This task is accomplished in part by the production of a large number of T lymphocytes, each bearing a different antigen receptor to match the enormous variety of antigens present in the microbial world. However, because antigen receptor diversity is generated by a random mechanism, the immune system must tolerate the function of T lymphocytes that by chance express a self-reactive antigen receptor. Therefore, during early development, T cells that are specific for antigens expressed in the thymus are physically deleted. The population of T cells that leaves the thymus and seeds the secondary lymphoid organs contains helpful cells that are specific for antigens from microbes but also potentially dangerous T cells that are specific for innocuous extrathymic self antigens.

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Effectiveness of Lipid and Lipidophilic Substances as Adjuvants

Cited by 136 publications

References 3 publications

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

The Ability of Bacterial Lipopolysaccharide to Modulate the Induction of Unresponsiveness to a State of Immunity

The anatomy of T-cell activation and tolerance.

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