Intrathymic T-cell migration: a combinatorial interplay of extracellular matrix and chemokines?

Savino, Wilson; Mendes-da-Cruz, Daniella Arêas; Silva, João; Dardenne, Mireille; Cotta-de-Almeida, Vinı́cius

doi:10.1016/s1471-4906(02)02224-x

Cited by 124 publications

(138 citation statements)

References 58 publications

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“…The hypothesis that HPAIV interferes with T lymphocyte development was supported by the findings that the expression of chemokines (CXCL12, CCL25) and cell adhesion molecules (ICAM-1, VCAM-1) involved in T cell development was drastically reduced after HPAIV but only slightly after H1N1v or H5N2 influenza virus infection. CXCL12, which is recognized by the CXCR4 receptor, is an essential prerequisite for functional thymocyte migration (33). CXCL12 is produced by both cortical and medullar epithelial cells, and recent studies underline the urgent need for CXCL12/CXCR4 pathway in T lymphocyte development in vivo (34).…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…The dynamics of thymocyte release from TNCs may be modulated by exogenous factors, including ECM proteins and antibodies recognizing either ECM or their receptors. 28,31 We have exploited this model to determine whether galectin-3 could modulate thymocyte-TEC interactions within the TNCs. Lymphoepithelial complexes obtained from either control or infected mice were cultured and exposed to specific stimuli for 12 hours.…”

Section: Galectin-3 Modulates Migration Of Thymocytesmentioning

confidence: 99%

Altered Expression of Galectin-3 Induces Cortical Thymocyte Depletion and Premature Exit of Immature Thymocytes during Trypanosoma cruzi Infection

Silva

Lorenzato

Nihei

et al. 2007

The American Journal of Pathology

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During acute infection with Trypanosoma cruzi, the causative agent of Chagas' disease, the thymus undergoes intense atrophy followed by a premature escape of CD4 ؉ CD8 ؉ immature cortical thymocytes. Here we report a pivotal role for the endogenous lectin galectin-3 in accelerating death of thymocytes and migration of these cells away from the thymus after T. cruzi infection. We observed a pronounced increase in galectin-3 expression that paralleled the extensive depletion of CD4 ؉ CD8 ؉ immature thymocytes after infection. In vitro, recombinant galectin-3 induced increased levels of death in cortical immature thymocytes. Consistent with the role of galectin-3 in promoting cell death, thymuses from gal-3 ؊/؊ mice did not show cortical thymocyte depletion after parasite infection in vivo. In addition, galectin-3 accelerated laminin-driven CD4 ؉ CD8 ؉ thymocyte migration in vitro and in vivo induced exportation of CD4 ؉ CD8 ؉ cells from the thymus to the peripheral compartment. Our findings provide evidence of a novel role for galectin-3 in the regulation of thymus physiology and identify a potential mechanism based on proteinglycan interactions in thymic atrophy associated with acute T. cruzi infection.

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“…The regulatory mechanisms involved in the control of thymic ECM production and degradation are poorly understood (reviewed in Ref. 42). Although some metalloproteinases have been shown to be constitutively expressed in human thymus (43) and transcripts for metalloproteinase-9 have also been detected in fetal mouse thymocyte precursors (44), their role in the physiological breakdown of thymic ECM remains unclear.…”

Section: Lymph Nodementioning

confidence: 99%

Cathepsin-L Influences the Expression of Extracellular Matrix in Lymphoid Organs and Plays a Role in the Regulation of Thymic Output and of Peripheral T Cell Number

Lombardi

Burzyn

Mundiñano

et al. 2005

The Journal of Immunology

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Nackt mice, which are deficient in cathepsin-L (CTSL), show an early impairment during positive selection in the context of class II MHC molecules and as a consequence, the percentage and absolute number of CD4+ thymocytes are significantly decreased. In this study, we show that lymph nodes from nackt mice are hypertrophied, showing normal absolute numbers of CD4+ T cells and marked increases in the number of CD8+ T lymphocytes. Basal proliferative levels are increased in the CD4+ but not in the CD8+ population. Lymph node T cells show increases in the expression of α5, α6, and β1 integrin chains. These alterations correlate with increases in the expression of extracellular matrix (ECM) components in lymph nodes. Interestingly, laminin, fibronectin, and collagen I and IV are markedly decreased in nackt thymus which shows an augmented output of CD8+ cells. These results demonstrate that a mutation in the Ctsl gene influences the levels of ECM components in lymphoid organs, the thymic output, and the number of T cells in the periphery. They further raise the possibility that, by regulating the level of expression of ECM components in lymphoid organs, CTSL is able to broadly affect the immune system.

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Intrathymic T-cell migration: a combinatorial interplay of extracellular matrix and chemokines?

Cited by 124 publications

References 58 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

Altered Expression of Galectin-3 Induces Cortical Thymocyte Depletion and Premature Exit of Immature Thymocytes during Trypanosoma cruzi Infection

Cathepsin-L Influences the Expression of Extracellular Matrix in Lymphoid Organs and Plays a Role in the Regulation of Thymic Output and of Peripheral T Cell Number

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