The role of thymic epithelium in the acquisition of tolerance

Houssaint, Elisabeth; Flajnik, Martin F.

doi:10.1016/0167-5699(90)90141-u

Cited by 35 publications

(19 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This finding suggests that some T cells recognizing minor H-Ag are still present in the recipient and can be activated to proliferate (Horton et al, 1993). This phenomenon, called “split” tolerance was first described for transplanted thymic epithelium in frogs, birds and mammals (Houssaint and Flajnik, 1990), and was shown to be induced in Xenopus larvae by non-thymic tissues such as skin (reviewed in Cohen et al, 1985). “Split” tolerance is considered to be a nondeletional type of tolerance involving MHC class II molecules (reviewed in Houssaint and Flajnik, 1990).…”

Section: Remodeling Of the Immune System During Metamorphosismentioning

confidence: 99%

“…This phenomenon, called “split” tolerance was first described for transplanted thymic epithelium in frogs, birds and mammals (Houssaint and Flajnik, 1990), and was shown to be induced in Xenopus larvae by non-thymic tissues such as skin (reviewed in Cohen et al, 1985). “Split” tolerance is considered to be a nondeletional type of tolerance involving MHC class II molecules (reviewed in Houssaint and Flajnik, 1990). Larvally-induced allotolerance is thymusdependent (Barlow and Cohen, 1983; Arnall and Horton, 1986, 1987).…”

Section: Remodeling Of the Immune System During Metamorphosismentioning

confidence: 99%

See 1 more Smart Citation

Comparative and developmental study of the immune system inXenopus

Robert

Ohta

2009

Developmental Dynamics

233

253

View full text Add to dashboard Cite

Xenopus laevis is the model of choice for evolutionary, comparative, and developmental studies of immunity, and invaluable research tools including MHC-defined clones, inbred strains, cell lines, and monoclonal antibodies are available for these studies. Recent efforts to use Silurana (Xenopus) tropicalis for genetic analyses have led to the sequencing of the whole genome. Ongoing genome mapping and mutagenesis studies will provide a new dimension to the study of immunity. Here we review what is known about the immune system of X. laevis integrated with available genomic information from S. tropicalis. This review provides compelling evidence for the high degree of similarity and evolutionary conservation between Xenopus and mammalian immune systems. We propose to build a powerful and innovative comparative biomedical model based on modern genetic technologies that takes take advantage of X. laevis and S. tropicalis, as well as the whole Xenopus genus.

show abstract

Section: Remodeling Of the Immune System During Metamorphosismentioning

confidence: 99%

Section: Remodeling Of the Immune System During Metamorphosismentioning

confidence: 99%

Comparative and developmental study of the immune system inXenopus

Robert

Ohta

2009

Developmental Dynamics

233

253

View full text Add to dashboard Cite

show abstract

“…Although the func tion o f the medullary epithelium is unclear, clonal deletion is manifest in this region (even if induced in the cortex) and the epithelium can induce tolerance in the form o f anergy [24][25][26]. Medullary epithelium also forms stromal cell complexes with thymocytes which may be maturation link ed [27,28] and possibly related to emigration [29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

The Murine Thymic Microenvironment: Changes with Age

Takeoka

Chen

Yago

et al. 1996

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Immunosenescence has been well described in both human and a variety of animal species and has an important influence on changes in immune function. Although several mechanisms may be operating to explain the alterations in immune function with age, one factor that has attracted significant attention has been the progressive age-dependent involution of the thymus. Hitherto, most studies of thymus have focused only on thymocytes. We have now taken advantage of a well-defined panel of monoclonal antibodies (mAbs called MTS) that recognize and characterize the thymic miroenvironment, including epithelial and nonepithelial elements. Recent data using these MTS mAbs have disclosed significant abnormalities in the thymic cortex in models of murine lupus including the unusual appearance of medullary-type epithelial cells in the cortical areas and the presence of epithelial free spaces or ‘cortical holes’. In this study, we investigated age-related changes in the thymic microenvironment in 12-month-old C3H/HeJ, C57BL/6 and BALB/c mice. Controls included thymus from young 4-to 6-week-old mice as well as 6-month-old BALB/c mice. As expected, the thymus of all 12-month-old mice manifested normal and distinctive separation of cortical and medullary epithelium. However, unlike younger mice, the 12-month-old mice had severe changes in these regions. For example, in older mice, the cortex and medulla were diffusely irregular and atrophic and had a poorly defined cortico medullary junction; the former having small disrupted epithelial networks, and the latter containing clusters of atrophic cells. Moreover, the extracellular matrix was increased and contained large irregularly shaped clusters. Interestingly, the thymus of 6-month-old mice expressed some changes within the medullary epithelium and the extracellular matrix, but the cortical epithelium remained unchanged. These age-related degenerative changes in the thymic microenvironment differ significantly from the abnormalities identified in autoimmunity and may be a factor in immunosenescence.

show abstract

“…The role of cortical epithelium in tolerance induction has been controversial (reviewed in [17–20]). Several experiments using thymus transplantation have clearly indicated that thymic epithelium exhibits toleragenic function [21–24].…”

Section: Introductionmentioning

confidence: 99%

TSCOT + Thymic Epithelial Cell-Mediated Sensitive CD4 Tolerance by Direct Presentation

et al. 2008

View full text Add to dashboard Cite

Although much effort has been directed at dissecting the mechanisms of central tolerance, the role of thymic stromal cells remains elusive. In order to further characterize this event, we developed a mouse model restricting LacZ to thymic stromal cotransporter (TSCOT)-expressing thymic stromal cells (TDLacZ). The thymus of this mouse contains approximately 4,300 TSCOT+ cells, each expressing several thousand molecules of the LacZ antigen. TSCOT+ cells express the cortical marker CDR1, CD40, CD80, CD54, and major histocompatibility complex class II (MHCII). When examining endogenous responses directed against LacZ, we observed significant tolerance. This was evidenced in a diverse T cell repertoire as measured by both a CD4 T cell proliferation assay and an antigen-specific antibody isotype analysis. This tolerance process was at least partially independent of Autoimmune Regulatory Element gene expression. When TDLacZ mice were crossed to a novel CD4 T cell receptor (TCR) transgenic reactive against LacZ (BgII), there was a complete deletion of double-positive thymocytes. Fetal thymic reaggregate culture of CD45- and UEA-depleted thymic stromal cells from TDLacZ and sorted TCR-bearing thymocytes excluded the possibility of cross presentation by thymic dendritic cells and medullary epithelial cells for the deletion. Overall, these results demonstrate that the introduction of a neoantigen into TSCOT-expressing cells can efficiently establish complete tolerance and suggest a possible application for the deletion of antigen-specific T cells by antigen introduction into TSCOT+ cells.

show abstract

The role of thymic epithelium in the acquisition of tolerance

Cited by 35 publications

References 42 publications

Comparative and developmental study of the immune system inXenopus

Comparative and developmental study of the immune system inXenopus

The Murine Thymic Microenvironment: Changes with Age

TSCOT + Thymic Epithelial Cell-Mediated Sensitive CD4 Tolerance by Direct Presentation

Contact Info

Product

Resources

About