Oral Tolerance: A Biologically Relevant Pathway to Generate Peripheral Tolerance against External and Self Antigens

2015 ◽  
pp. 259-290 ◽  
Author(s):  
Aharon Friedman ◽  
Ahmad Al-Sabbagh ◽  
Leonilda M. B. Santos ◽  
Jacqueline Fishman-Lobell ◽  
Malu Polanski ◽  
...  
Keyword(s):  
Oral Tolerance ◽  
Peripheral Tolerance ◽  
Biologically Relevant ◽  
Self Antigens

Oral Tolerance: A Biologically Relevant Pathway to Generate Peripheral Tolerance against External and Self Antigens (Part 2 of 2)

1994 ◽  
pp. 275-290
Author(s):  
Aharon Friedman ◽  
Ahmad Al-Sabbagh ◽  
Leonilda M.B. Santos ◽  
Jacqueline Fishman-Lobell ◽  
Malu Polanski ◽  
...  
Keyword(s):  
Oral Tolerance ◽  
Peripheral Tolerance ◽  
Biologically Relevant ◽  
Self Antigens

Oral Tolerance: A Biologically Relevant Pathway to Generate Peripheral Tolerance against External and Self Antigens (Part 1 of 2)

1994 ◽  
pp. 259-274 ◽  
Author(s):  
Aharon Friedman ◽  
Ahmad Al-Sabbagh ◽  
Leonilda M.B. Santos ◽  
Jacqueline Fishman-Lobell ◽  
Malu Polanski ◽  
...  
Keyword(s):  
Oral Tolerance ◽  
Peripheral Tolerance ◽  
Biologically Relevant ◽  
Self Antigens

scholarly journals Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens

2021 ◽  
Vol 12 ◽  
Author(s):  
Giovanna Flores-Mendoza ◽  
Noé Rodríguez-Rodríguez ◽  
Rosa M. Rubio ◽  
Iris K. Madera-Salcedo ◽  
Florencia Rosetti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Peripheral Tolerance ◽  
Tolerance Mechanism ◽  
Genetic Deficiency ◽  
Self Antigen ◽  
Insight Into ◽  
Self Antigens

Activation of self-reactive CD8+ T cells induces a peripheral tolerance mechanism that involves loss of CD8 expression. Because genetic deficiency of Fas and Fasl causes the accumulation of double-negative (DN; CD3+ TCR-αβ+ CD4- CD8-) T cells that have been proposed to derive from CD8+ cells, we decided to explore the role of Fas and FasL in self-antigen-induced CD8 downregulation. To this end, we quantified Fas and FasL induction by different stimuli and analyzed the effects of Fas/FasL deficiency during a protective immune response and after exposure to self-antigens. Our data describes how Fas and FasL upregulation differs depending on the setting of CD8 T cell activation and demonstrates that Fas/FasL signaling maintains CD8 expression during repetitive antigen stimulation and following self-antigen encounter. Together, our results reveal an unexpected role of Fas/FasL signaling and offer a new insight into the role of these molecules in the regulation of immune tolerance.

scholarly journals The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance

2005 ◽  
Vol 201 (10) ◽  
pp. 1615-1625 ◽  
Author(s):  
Hsi-Hsien Lin ◽  
Douglas E. Faunce ◽  
Martin Stacey ◽  
Ania Terajewicz ◽  
Takahiko Nakamura ◽  
...  
Keyword(s):  
Oral Tolerance ◽  
Low Dose ◽  
Peripheral Tolerance ◽  
Delayed Type Hypersensitivity ◽  
Mouse Macrophage ◽  
Immune Deviation ◽  
Dose Oral ◽  
Tolerance Model

We show that the mouse macrophage-restricted F4/80 protein is not required for the development and distribution of tissue macrophages but is involved in the generation of antigen-specific efferent regulatory T (T reg) cells that suppress antigen-specific immunity. In the in vivo anterior chamber (a.c.)–associated immune deviation (ACAID) model of peripheral tolerance, a.c. inoculation of antigen into F4/80−/− mice was unable to induce efferent T reg cells and suppress delayed-type hypersensitivity (DTH) responses. Moreover, the use of anti-F4/80 mAb and F4/80−/− APCs in an in vitro ACAID model showed that all APC cells in the culture must be able to express F4/80 protein if efferent T reg cells were to be generated. In a low-dose oral tolerance model, WT but not F4/80−/− mice generated an efferent CD8+ T reg cell population that suppressed an antigen-specific DTH response. Peripheral tolerance was restored in F4/80−/− mice by adoptive transfer of F4/80+ APCs in both peripheral tolerance models, indicating a central role for the F4/80 molecule in the generation of efferent CD8+ T reg cells.

Regulation of Autoreactive T Cell Function by Oral Tolerance to Self-Antigens

2004 ◽  
Vol 1029 (1) ◽  
pp. 172-179 ◽  
Author(s):  
CAROLINE C. WHITACRE ◽  
FEI SONG ◽  
RICHARD M. WARDROP ◽  
KIM CAMPBELL ◽  
MELANIE McCLAIN ◽  
...  
Keyword(s):  
T Cell ◽  
Oral Tolerance ◽  
Cell Function ◽  
Autoreactive T Cell ◽  
T Cell Function ◽  
Self Antigens

scholarly journals P03.07 Analysis of scRNAseq from the human thymus nominates genes potentially missing from central tolerance of cytotoxic T cells

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A15.2-A16
Author(s):  
L Blumenberg ◽  
G Atwal ◽  
A Dhanik
Keyword(s):  
T Cells ◽  
T Cell ◽  
Negative Selection ◽  
Cytotoxic T Cells ◽  
Peripheral Tolerance ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Human Thymus ◽  
Part Time ◽  
Self Antigens

BackgroundDuring thymic development, cytotoxic T cells that can bind to and attack self antigens undergo negative selection thus preventing damage to the self tissues. The sparse medullar thymic epithelial cells (mTECs) present in the thymus are responsible for presenting self antigens to T cells so that they can trigger apoptosis or differentiation into non-cytotoxic lineages if they bind too strongly.Materials and MethodsUnderstanding gene expression in mTECs is essential for understanding the shape of the human T cell receptor repertoire, which is key for current and emerging cancer immunotherapies. Recent availability of human thymus single cell RNAseq (scRNAseq) data provides an extremely high-resolution view into the pattern of expression within this critical cell type. To determine which epitopes have had to opportunity to be presented during T cell negative selection, we analyzed the human thymus scRNAseq dataset to establish which genes are expressed in mTECs and therefore subject to central tolerance.ResultsThe coverage of the whole transcriptome of a particular cell is generally sparse. It is therefore difficult to understand basic features of individual cells or cell types such as how many genes are expressed. We used cell- and read-level subsampling to estimate whether a sufficient number of cells and reads had been captured to support categorizing a gene as non-expressed in mTECs. We also examined the expression of the genes not expressed in mTECs in other healthy tissues, and found their expression was almost exclusively restricted to the testis (an immune-privileged site) and the liver (a site of peripheral tolerance)ConclusionsAltogether, these analyses establish a strategy for determining if a data set has sufficient depth to estimate the total number of genes expressed and secondly define a key list of genes that are not expressed during central tolerization of T cells, which represent a compelling list of possible cancer immunotherapy targets.Disclosure InformationL. Blumenberg: A. Employment (full or part-time); Significant; Regeneron Pharmaceuticals. G. Atwal: A. Employment (full or part-time); Significant; Regeneron Pharmaceuticals. A. Dhanik: A. Employment (full or part-time); Significant; Regeneron Pharmaceuticals.

scholarly journals CD11b facilitates the development of peripheral tolerance by suppressing Th17 differentiation

2007 ◽  
Vol 204 (7) ◽  
pp. 1519-1524 ◽  
Author(s):  
Driss Ehirchiou ◽  
Ying Xiong ◽  
Guangwu Xu ◽  
Wanjun Chen ◽  
Yufang Shi ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Oral Tolerance ◽  
Cell Activation ◽  
Cell Lineage ◽  
Peripheral Tolerance ◽  
T Helper 17 ◽  
Opposing Effects ◽  
Antigen Presenting

Antigen-induced immune suppression, like T cell activation, requires antigen-presenting cells (APCs); however, the role of APCs in mediating these opposing effects is not well understood, especially in vivo. We report that genetic inactivation of CD11b, which is a CD18 subfamily of integrin receptors that is highly expressed on APCs, abolishes orally induced peripheral immune tolerance (oral tolerance) without compromising APC maturation or antigen-specific immune activation. The defective oral tolerance in CD11b−/− mice can be restored by adoptive transfer of wild-type APCs. CD11b deficiency leads to enhanced interleukin (IL) 6 production by APCs, which subsequently promotes preferential differentiation of naive T cells to T helper 17 (Th17) cells, which are a T cell lineage characterized by their production of IL-17. Consequently, antigen feeding and immunization of CD11b−/− mice results in significant production of IL-17 within the draining lymph nodes that interferes with the establishment of oral tolerance. Together, we conclude that CD11b facilitates oral tolerance by suppressing Th17 immune differentiation.

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