The impact of circulating dendritic cells on the development and differentiation of thymocytes

Proietto, Anna I; Dommelen, Serani van; Wu, Li

doi:10.1038/icb.2008.86

Cited by 45 publications

(51 citation statements)

References 73 publications

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“…In a second step, DCs move further on into the thymus, where influenza virus-infected DCs first reach the corticomedullary junction and the medulla, the place of negative selection processes. Thymic APCs in the thymus, namely DCs, but also thymic epithelial cells, are responsible for the selection processes (47). We conclude that CD45 2 epithelial cells in the medulla are the first target for infection because viral footprints in the CD45 + thymocyte population were absent (data not shown).…”

Section: Discussionmentioning

confidence: 79%

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

Vogel

Haasbach

Reiling

et al. 2010

The Journal of Immunology

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Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in humans. Still, the basis for their increased pathogenesis remains unclear. Additionally, the high morbidity in the younger population stays inexplicable, and the recent pandemic H1N1v outbreak in 2009 demonstrated the urgent need for a better understanding about influenza virus infection. In the present study, we demonstrated that HPAIV infection of mice not only led to lung destruction but also to functional damage of the thymus. Moreover, respiratory dendritic cells in the lung functioned as targets for HPAIV infection being able to transport infectious virus from the lung into the thymus. The pandemic H1N1 influenza virus was able to infect respiratory dendritic cells without a proper transport to the thymus. The strong interference of HPAIV with the immune system is especially devastating for the host and can lead to lymphopenia. In summary, from our data, we conclude that highly pathogenic influenza viruses are able to reach the thymus via dendritic cells and to interfere with T lymphocyte development. Moreover, this exceptional mechanism might not only be found in influenza virus infection, but also might be the reason for the increased immune evasion of some new emerging pathogens.

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Section: Discussionmentioning

confidence: 79%

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

Vogel

Haasbach

Reiling

et al. 2010

The Journal of Immunology

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“…34 Peripheral dendritic cells that migrate into the thymus, as well as resident intrathymic dendritic cells and thymic epithelial cells, together or individually, mediate the development of antigenspecific central tolerance. 35 Additional studies are required to determine what cells are transduced after neonatal gene delivery and to understand the mechanisms involved in how these cells participate in the induction of central tolerance to FVIII.…”

Section: Discussionmentioning

confidence: 99%

A murine model for induction of long-term immunologic tolerance to factor VIII does not require persistent detectable levels of plasma factor VIII and involves contributions from Foxp3+ T regulatory cells

Matsui

Shibata

Brown

et al. 2009

Blood

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Under certain instances, factor VIII (FVIII) stimulates an immune response, and the resulting neutralizing antibodies present a significant clinical challenge. Immunotherapies to re-establish or induce longterm tolerance would be beneficial, and an in-depth knowledge of mechanisms involved in tolerance induction is essential to develop immune-modulating strategies. We have developed a murine model system for studying mechanisms involved in induction of immunologic tolerance to FVIII in hemophilia A mice. We

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“…Primers and probes for the detection were employed following the methods described in previous reports (21,33).…”

Section: Chemokine and Chemokine Receptor Expressionmentioning

confidence: 99%

NF-κB–Inducing Kinase in Thymic Stroma Establishes Central Tolerance by Orchestrating Cross-Talk with Not Only Thymocytes but Also Dendritic Cells

Mouri

Nishijima

Kawano

et al. 2014

The Journal of Immunology

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Essential roles of NF-κB–inducing kinase (NIK) for the development of medullary thymic epithelial cells (mTECs) and regulatory T cells have been highlighted by studies using a strain of mouse bearing a natural mutation of the NIK gene (aly mice). However, the exact mechanisms underlying the defect in thymic cross-talk leading to the breakdown of self-tolerance in aly mice remain elusive. In this study, we demonstrated that production of regulatory T cells and the final maturation process of positively selected conventional αβ T cells are impaired in aly mice, partly because of a lack of mature mTECs. Of note, numbers of thymic dendritic cells and their expression of costimulatory molecules were also affected in aly mice in a thymic stroma–dependent manner. The results suggest a pivotal role of NIK in the thymic stroma in establishing self-tolerance by orchestrating cross-talk between mTECs and dendritic cells as well as thymocytes. In addition, we showed that negative selection was impaired in aly mice as a result of the stromal defect, which accounts for the development of organ-specific autoimmunity through a lack of normal NIK.

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The impact of circulating dendritic cells on the development and differentiation of thymocytes

Cited by 45 publications

References 73 publications

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

A murine model for induction of long-term immunologic tolerance to factor VIII does not require persistent detectable levels of plasma factor VIII and involves contributions from Foxp3+ T regulatory cells

NF-κB–Inducing Kinase in Thymic Stroma Establishes Central Tolerance by Orchestrating Cross-Talk with Not Only Thymocytes but Also Dendritic Cells

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