Tolerogenicity of resting and activated B cells.

Gilbert, Kathleen M.; Weigle, William O.

doi:10.1084/jem.179.1.249

Cited by 81 publications

(47 citation statements)

References 50 publications

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“…Induction of tolerthe absence of costimulation. Small B lymphocytes express only low levels of the B7-1/2 costimulatory molecules on ance using intrathymic peptides appeared to be mediated by the induction of T-cell anergy because the tolerant their surface; unless stimulated, they are ineffective as APC (116,158,296). Small B cells induce tolerance when acting state could be broken by administration of exogenous IL-2 (26, 235).…”

Section: Methods To Induce Transplantation Generalized Immunosuppmentioning

confidence: 99%

Induction of Immunologic Tolerance for Transplantation

Rossini

Greiner

Mordes

1999

Physiological Reviews

121

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Rossini, Aldo A., Dale L. Greiner, and John P. Mordes. Induction of Immunologic Tolerance for Transplantation. Physiol. Rev. 79: 99–141, 1999. — In the second half of the 20th century, the transplantation of replacement organs and tissues to cure disease has become a clinical reality. Success has been achieved as a direct result of progress in understanding the cellular and molecular biology of the immune system. This understanding has led to the development of immunosuppressive pharmaceuticals that are part of nearly every transplantation procedure. All such drugs are toxic to some degree, however, and their chronic use, mandatory in transplantation, predisposes the patient to the development of infection and cancer. In addition, many of them may have deleterious long-term effects on the function of grafts. New immunosuppressive agents are constantly under development, but organ transplantation remains a therapy that requires patients to choose between the risks of their primary illness and its treatment on the one hand, and the risks of life-long systemic immunosuppression on the other. Alternatives to immunosuppression include modulation of donor grafts to reduce immunogenicity, removal of passenger leukocytes, transplantation into immunologically privileged sites like the testis or thymus, encapsulation of tissue, and the induction of a state of immunologic tolerance. It is the last of these alternatives that has, perhaps, the most promise and most generic applicability as a future therapy. Recent reports documenting long-term graft survival in the absence of immunosuppression suggest that tolerance-based therapies may soon become a clinical reality. Of particular interest to our laboratory are transplantation strategies that focus on the induction of donor-specific T-cell unresponsiveness. The basic biology, protocols, experimental outcomes, and clinical implications of tolerance-based transplantation are the focus of this review.

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Section: Methods To Induce Transplantation Generalized Immunosuppmentioning

confidence: 99%

Induction of Immunologic Tolerance for Transplantation

Rossini

Greiner

Mordes

1999

Physiological Reviews

121

View full text Add to dashboard Cite

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“…Recently, it was shown that on a per cell basis B lymphocytes are as effective as DC in activating naive T cells [4] and that B lymphocytes and DC undergo a similar increment of peptide/MHC Class II complexes after intravenous injection of antigen [5]. In spite of this evidence, several reports indicate that B lymphocytes fail to activate naive T cells [6,7].…”

Section: Introductionmentioning

confidence: 99%

CD8 T cell priming by B lymphocytes is CD4 help dependent

Castiglioni¹,

Gerloni²,

Cortez-Gonzalez³

et al. 2005

Eur J Immunol

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While it is generally accepted that B lymphocytes can present antigen and activate CD4 T cells, priming of CD8 T cells by B lymphocytes remains controversial. Recently, we showed that mice injected with genetically programmed B lymphocytes generate antigen specific CD4 and CD8 T cell responses in vivo that could also be induced in mice lacking functional dendritic cells. To gain further insights into the requirements for T cell priming by antigen-presenting B lymphocytes, in vitro experiments were performed using ovalbumin (OVA) and OVA-specific TCR-transgenic CD4 and CD8 T cells. We found that while B lymphocytes can directly prime CD4 T cells, the activation of CD8 T cells requires T cell help. Transfer experiments show that help can either be contact dependent or be mediated by soluble factors in the supernatants of activated OVAspecific CD4 T cells. Furthermore, the effect of activated CD4 T cells can be replaced by soluble recombinant IL-4. Collectively, the data show the existence of different requirements for priming of CD4 and CD8 T cells and point to the previously unappreciated fact that the induction of CD8 T cell responses by B lymphocytes requires T cell help.

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“…Because resting B cells are known to express low levels of costimulatory molecules and can tolerize the T cells (5,11,12), we therefore used activated B cells as APC for our study. It is known that B cell activation may occur in response to two kinds of Ags, T-dependent and T-independent Ags (13).…”

Section: B Cells Are Known To Play An Important Role In Cd4mentioning

confidence: 99%

B Cells Activated by Lipopolysaccharide, But Not By Anti-Ig and Anti-CD40 Antibody, Induce Anergy in CD8+ T Cells: Role of TGF-β1

Parekh

Prasad

Banerjee

et al. 2003

The Journal of Immunology

201

136

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B cells recognize Ag through their surface IgRs and present it in the context of MHC class II molecules to CD4+ T cells. Recent evidence indicates that B cells also present exogenous Ags in the context of MHC class I to CD8+ T cells and thus may play an important role in the modulation of CTL responses. However, in this regard, conflicting reports are available. One group of studies suggests that the interaction between B cells and CD8+ T cells leads to the activation of the T cells, whereas other studies propose that it induces T cell tolerance. For discerning this dichotomy, we used B cells that were activated with either LPS or anti-Ig plus anti-CD40 Ab, which mimic the T-independent and T-dependent modes of B cell activation, respectively, to provide accessory signals to resting CD8+ T cells. Our results show that, in comparison with anti-Ig plus anti-CD40 Ab-activated B cells, the LPS-activated B cells (LPS-B) failed to induce significant levels of proliferation, cytokine secretion, and cytotoxic ability of CD8+ T cells. This hyporesponsiveness of CD8+ T cells activated with LPS-B was significantly rescued by anti-TGF-β1 Ab. Moreover, it was found that such hyporesponsive CD8+ T cells activated with LPS-B had entered a state of anergy. Furthermore, LPS-B expresses a significantly higher level of TGF-β1 on the surface, which caused the observed hyporesponsiveness of CD8+ T cells. Therefore, this study, for the first time, provides a novel mechanism of B cell surface TGF-β1-mediated hyporesponsiveness leading to anergy of CD8+ T cells.

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Tolerogenicity of resting and activated B cells.

Cited by 81 publications

References 50 publications

Induction of Immunologic Tolerance for Transplantation

Induction of Immunologic Tolerance for Transplantation

CD8 T cell priming by B lymphocytes is CD4 help dependent

B Cells Activated by Lipopolysaccharide, But Not By Anti-Ig and Anti-CD40 Antibody, Induce Anergy in CD8+ T Cells: Role of TGF-β1

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