Conversion of tumor-specific CD4+ T-cell tolerance to T-cell priming through in vivo ligation of CD40

10.1038/10503 ◽  
1999 ◽  
Vol 5 (7) ◽  
pp. 780-787 ◽  
Author(s):  
Eduardo M. Sotomayor ◽  
Ivan Borrello ◽  
Erev Tubb ◽  
Frédérique-Marie Rattis ◽  
Harold Bien ◽  
...  
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
T Cell Priming

CD40 stimulation in vivo does not inhibit CD4+ T cell tolerance to soluble antigens

2002 ◽  
Vol 84 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Jiaren Sun ◽  
Nancy Van Houten
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Cd40 Stimulation

Induction of antigen-specific CD4+ T-cell anergy and deletion by in vivo viral gene transfer

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 969-977 ◽  
Author(s):  
Eric Dobrzynski ◽  
Federico Mingozzi ◽  
Yi-Lin Liu ◽  
Elisabeth Bendo ◽  
Ou Cao ◽  
...  
Keyword(s):  
T Cell ◽  
Gene Transfer ◽  
Cell Receptor ◽  
Cd4 T Cell ◽  
Viral Gene ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Viral Gene Transfer

AbstractImmune responses to the therapeutic gene product are a potentially serious complication in treatment of genetic disease by gene therapy. Induction and maintenance of immunologic hypo-responsiveness to the therapeutic antigen is therefore critical to the success of gene-based treatment of inherited protein deficiency. Here, we demonstrate induction of antigen-specific CD4+ T-cell tolerance to a secreted transgene product (ovalbumin, ova) in ova-specific T-cell receptor (TCR) transgenic mice by hepatic adeno-associated virus (AAV)–mediated gene transfer. Transduced mice maintained stable circulating ova levels without evidence of an immune response. Lymph node cells and splenocytes were hypo-responsive to ova as early as day 10 after gene transfer. Numbers of TCR+CD4+ cells were reduced in secondary lymphoid organs and in the thymus by 1 to 2 months after vector administration. The remaining TCR+CD4+ cell population was anergic to ova antigen in vitro and enriched for CD25+ cells. These data provide direct evidence that transgene expression following in vivo viral gene transfer can induce CD4+ T-cell tolerance to the transgene product, involving anergy and deletion mechanisms.

scholarly journals Peripheral CD4+T-cell tolerance is induced in vivo by rare antigen-bearing B cells in follicular, marginal zone, and B-1 subsets

2013 ◽  
Vol 43 (7) ◽  
pp. 1818-1827 ◽  
Author(s):  
Susan E. Murray ◽  
Katelynne Gardner Toren ◽  
David C. Parker
Keyword(s):  
T Cell ◽  
B Cells ◽  
Marginal Zone ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance

ANTIGEN PRESENTATION BY EPIDERMAL LANGERHANS CELLS INDUCES CD4 T CELL TOLERANCE IN VIVO

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 179
Author(s):  
E Shklovskaya ◽  
D Gracey ◽  
B Fazekas de St. Groth
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Langerhans Cells ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Epidermal Langerhans Cells

scholarly journals LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5532-5540 ◽  
Author(s):  
Carrie L. Lucas ◽  
Creg J. Workman ◽  
Semir Beyaz ◽  
Samuel LoCascio ◽  
Guiling Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tolerance Induction ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Inhibitory Molecules ◽  
Mixed Chimeras

Abstract Administration of a single dose of anti-CD40L mAb at the time of allogeneic BM transplantation tolerizes peripheral alloreactive T cells and permits establishment of mixed hematopoietic chimerism in mice. Once engrafted, mixed chimeras are systemically tolerant to donor Ags through a central deletion mechanism and will accept any donor organ indefinitely. We previously found that the PD-1/PD-L1 pathway is required for CD8 T-cell tolerance in this model. However, the cell population that must express PD-1 and the role of other inhibitory molecules were unknown. Here, we report that LAG-3 is required for long-term peripheral CD8 but not CD4 T-cell tolerance and that this requirement is CD8 cell-extrinsic. In contrast, adoptive transfer studies revealed a CD8 T cell–intrinsic requirement for CTLA4/B7.1/B7.2 and for PD-1 for CD8 T-cell tolerance induction. We also observed that both PD-L1 and PD-L2 are independently required on donor cells to achieve T-cell tolerance. Finally, we uncovered a requirement for TGF-β signaling into T cells to achieve peripheral CD8 but not CD4 T-cell tolerance in this in vivo system.

scholarly journals In Vivo CD4+ T Cell Tolerance Induction Versus Priming Is Independent of the Rate and Number of Cell Divisions

2000 ◽  
Vol 164 (2) ◽  
pp. 649-655 ◽  
Author(s):  
Adam J. Adler ◽  
Ching-Tai Huang ◽  
Gregory S. Yochum ◽  
David W. Marsh ◽  
Drew M. Pardoll
Keyword(s):  
T Cell ◽  
Tolerance Induction ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Cell Divisions

scholarly journals TRANCE, a Tumor Necrosis Factor Family Member Critical for CD40 Ligand–independent T Helper Cell Activation

1999 ◽  
Vol 189 (7) ◽  
pp. 1025-1031 ◽  
Author(s):  
Martin F. Bachmann ◽  
Brian R. Wong ◽  
Régis Josien ◽  
Ralph M. Steinman ◽  
Annette Oxenius ◽  
...  
Keyword(s):  
T Cell ◽  
Family Member ◽  
T Cell Responses ◽  
Cd40 Ligand ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
T Cell Priming ◽  
Deficient Mice ◽  
Necrosis Factor

CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4+ T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4+ T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4+ T cell responses that produce normal levels of interferon γ, suggesting a CD40L/CD40-independent mechanism of CD4+ T cell priming that to date has not been elucidated. Here we show that CD4+ T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE/TRANCE-R interaction provides costimulation required for efficient CD4+ T cell priming during viral infection in the absence of CD40L/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4+ T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel and important target for immune intervention.

scholarly journals Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation

2018 ◽  
Vol 19 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Ludger Klein ◽  
Ellen A. Robey ◽  
Chyi-Song Hsieh
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Regulatory T Cell ◽  
T Cell Differentiation ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance
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