Phagocytosis of the Antigen, a Crucial Step in the Induction of the Primary Response

Frei, P.C.; Benacerraf, Baruj; Thorbecke, G. J.

doi:10.1073/pnas.53.1.20

Cited by 177 publications

(53 citation statements)

References 9 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: 95%

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: 95%

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

Wang

Davies

2007

International Immunopharmacology

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“…The net result of antigen administration is probably a balance between antibody production and tolerance, yet it may be di~cult to achieve or detect tolerance under conditions which greatly favor antibody production. The relative lack of tolerance observed in the NZB and B/W mice could reflect an abnormality in either the afferent or the efferent portion of the immune system, tending to favor an immune response to an antigen which, in other strains, was tolerogenic, The antigens used in our studies were ultracen-trifuged heterologous gamma globulins which produce a state of unresponsiveness because they are probably poorly phagocytized by ceils of the reticuloendothelial system (20). The nonphagocytized antigen may then interact directly with receptors on the lymphocyte to induce a state of immunologic unresponsiveness.…”

Section: Ttgg-hmaegglutination--hemagglutination Data (Figs 9 and 1mentioning

confidence: 99%

Relative Inability to Induce Tolerance in Adult NZB and NZB/NZW F1 Mice

Staples

Talal

1969

The Journal of Experimental Medicine

129

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Immunologic tolerance to ultracentrifuged bovine gamma globulin could not be induced in 6-wk old NZB or B/W mice, but developed readily in C3H, NZW, and C57Bl mice. NZB and B/W mice, as well as Balb/c mice, failed to become tolerant to ultracentrifuged human gamma globulin. The NZB and B/W mice also showed higher antibody titers to a standard antigenic challenge. This immunologic hyperreactivity and lack of experimental tolerance may be related to the lack of self-tolerance, autoimmunity, and lymphomas that develop in these mice at a later age.

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“…Evidence for the critical role of macrophages in the initiation of immune responses was provided by a study with Frei and Thorbecke. We demonstrated that whereas the intravenous injection of bovine serum albumin (BSA) to rabbits was uniformly immunogenic, BSA preparations from which their readily phagocytizable fraction had been removed by previous biological filtratioB in a rabbit were no longer immunogenic, but rather tolerogenic (23). This result may be related to the more recent experiments on the relative abilities of macrophagesj dendritic cells vs B cells to initiate T-cell responses, rather than to tolerize these cells.…”

Section: Cellular Immune Reactions First Evidence That Cellularmentioning

confidence: 51%

When All Is Said And Done..

Benacerraf¹

1991

Annual Review of Immunology

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Dr. Benacerraf describes his experience in training immunologists for a period of over 30 years. He then analyzes the circumstances in which selected discoveries were made in his laboratory and the events and reason ing that led to these findings. The following topics are discussed: The phagocytic activity of the reticulo-endothelial system. The pathogenesis of immune complex diseases. The impact of activated macrophages on tumor rejection. The evidence that T-ceII immunity is specific for internal protein determinants generated by antigen processing. The maturation of the antibody response in terms of antibody affinity. The discovery of Ir gene control of specific immune responses and the role of MHC molecules as presenters of peptide antigens to T cells. The generation of alloreactivity.Lastly, he addresses the administration of science and, particularly, the problems related to the transfer of technology to industrial partners.

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Phagocytosis of the Antigen, a Crucial Step in the Induction of the Primary Response

Cited by 177 publications

References 9 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

Relative Inability to Induce Tolerance in Adult NZB and NZB/NZW F1 Mice

When All Is Said And Done..

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