Delineation of Signals Required for Thymocyte Positive Selection

Santori, Fabio R.; Vukmanović, Stanislav

doi:10.4049/jimmunol.173.9.5517

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…During development, both B-and T-lymphocytes undergo a process of negative selection or tolerance induction in the bone marrow, and thymus, respectively, to prevent autoreactive lymphocytes (reacts against self-antigens) from gaining immune competence (Rolink et al, 2001;Santori and Vukmanovic, 2004;Huseby et al, 2005;Gallegos and Bevan, 2006). In spite of this, presence of product-related impurities (aggregates, deamidated or oxidized material, clipped protein) or contaminants with adjuvant properties such as host cell proteins, endotoxin, or oligonucleotides (Wadhwa et al, 1999), in recombinant or human-derived drug preparations, may lead to the activation of mature B1 lymphocytes and marginal zone B-lymphocytes.…”

Section: Mechanismmentioning

confidence: 99%

Immunogenicity of Biotherapeutics—An Overview

Subramanyam

2006

Journal of Immunotoxicology

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With the recent increase in the approval and use of biotherapeutics in clinical practice, management of the development of anti-drug antibodies (ADA) has become a key issue for effective long-term use of these drugs. In most instances, the clinical benefit derived from the use of the therapeutics outweighs the risk of developing ADA. In rare instances, however, safety issues accompany development of ADA. Although it is unclear why certain individuals generate an immune response while others tolerate the drug, growing experience from the clinic has facilitated a better appreciation of many patient-, disease- and product-related factors that contribute to immunogenicity. Furthermore, improvements in protein production, purification and delivery methods along with use of humanized or fully human recombinant proteins have helped to reduce the rates of immunogenicity considerably. This document provides an overview of the scientific reasons for developing an immunogenic response, factors that contribute to the immunogenicity of biotherapeutics, clinical impact of immunogenicity and general strategies used to manage this risk.

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Section: Mechanismmentioning

confidence: 99%

Immunogenicity of Biotherapeutics—An Overview

Subramanyam

2006

Journal of Immunotoxicology

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T cell receptor and cytokine signal integration in CD8+ T cells is mediated by the protein Themis

et al. 2020

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Absence of CD47 in vivo influences thymic dendritic cell subset proportions but not negative selection of thymocytes

Guimont-Desrochers

Beauchamp

Chabot‐Roy

et al. 2009

International Immunology

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CD47 is a ubiquitously expressed molecule which has been attributed a role in many cellular processes. Its role in preventing cellular phagocytosis has defined CD47 as an obligatory self-molecule providing a 'don't-eat-me-signal'. Additionally, CD47-CD172a interactions are important for cellular trafficking. Yet, the contribution of CD47 to T cell stimulation remains controversial, acting sometimes as a co-stimulator and sometimes as an inhibitor of TCR signalling or peripheral T cell responses. Most of the experiments leading to this controversy have been carried in in vitro systems. Moreover, the role of CD47 on thymocyte differentiation, which precisely relies on TCR signal strength, has not been evaluated. Here, we examine the in vivo role of CD47 in T cell differentiation using CD47-deficient mice. We find that, in the absence of CD47, thymocyte positive and negative selection processes are not altered. Indeed, our data demonstrate that the absence of CD47 does not influence the strength of TCR signalling in thymocytes. Furthermore, in agreement with a role for CD47-CD172a interactions in CD172a(+) dendritic cell migration, we report a reduced proportion of thymic dendritic cells expressing CD172a in CD47-deficient mice. As the total proportion of dendritic cells is maintained, this creates an imbalance in the proportion of CD172a(+) and CD172a(low) dendritic cells in the thymus. Together, these data indicate that the altered proportion of thymic dendritic cell subsets does not have a primordial influence on thymic selection processes.

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Delineation of Signals Required for Thymocyte Positive Selection

Cited by 3 publications

References 43 publications

Immunogenicity of Biotherapeutics—An Overview

Immunogenicity of Biotherapeutics—An Overview

T cell receptor and cytokine signal integration in CD8+ T cells is mediated by the protein Themis

Absence of CD47 in vivo influences thymic dendritic cell subset proportions but not negative selection of thymocytes

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