Lymphoid organs contain diverse cells expressing self-molecules

Access through your institution Buy or subscribe Derbinski _et al_.1 reported the expression of self-molecules in the mouse thymus. Their work follows earlier reports showing that

self-molecules with tissue-restricted expression (or “peripheral” proteins) are also produced in the thymus through “ectopic” or “promiscuous” transcription and translation2,3,4,5 and that

such expression contributes to shaping a self-tolerant T cell repertoire6. Derbinski _et al_. used RT-PCR to detect peripheral protein transcripts in thymic cell populations purified by

fluorescence-activated cell sorting after staining with markers specific for medullar or cortical thymic epithelial cells (mTECs and cTECs, respectively) and for bone marrow–derived APCs

such as macrophages and DCs. Essentially all the molecules studied—including several autoantigens involved in autoimmune diseases such as type I diabetes and multiple sclerosis—were

expressed by mTECs and not by DCs or macrophages. These findings contrast with earlier reports3,5, which showed that thymic cells expressing type I diabetes autoantigens (proinsulin and

insulin, GAD and IA-2 and other pancreatic hormones) had surface markers that are typical of DCs and macrophages in human and mouse thymi, respectively. In our experiments,

immunohistochemistry and double-immunofluorescence techniques were used to stain frozen tissue sections5. This approach prevents the detection of artifacts potentially associated with tissue

processing and cell manipulation and allows the examination of cells in their native state. Unlike Derbinski _et al_.1, but like Throsby _et al_.3, we were unable to colocalize proinsulin,

GAD and IA-2 with cytokeratin (a marker of thymic epithelial cells)5. We were also unable to colocalize proinsulin with AIRE5, which is expressed in thymic epithelial cells and a subset of

DCs7. If our findings were based on staining artifacts, we would have double-stained for cytokeratin and AIRE as well. In addition, we detected similar cells expressing proinsulin, GAD and

IA-2 in peripheral lymphoid tissues, which also expressed the transcripts encoding these molecules5,8. As the spleen and lymph nodes do not contain thymic epithelial cells, at least some of

the bone marrow–derived APCs expressing peripheral proteins in lymphoid tissues should transcribe the corresponding genes. Accordingly, we detected insulin mRNA in proinsulin+CD11c+ DCs

after the cells were sorted from human spleen and showed that similar cells expressing proinsulin existed in peripheral blood9. In contrast, Derbinski _et al_. did not detect insulin, GAD or

IA-2 transcripts in RNA samples from splenic CD11c+ DCs. This may reflect methodological differences, as we enriched our DC preparations by costaining for CD11c and proinsulin. This is a

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during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Derbinski, J., Schulte, A., Kyewski, B.

& Klein, L. _Nature Immunol._ 2, 1032–1039 (2001). Article  CAS  Google Scholar  * Smith, K. M., Olson, D. C., Hirose, R. & Hanahan, D. _Int. Immunol._ 9, 1355–1365 (1997). Article 

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J. & Pugliese, A. http://207.78.21.41./am01/AnnualMeeting/ Abstracts/NumberResults,asp?idAbs=18-LB (2001). Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Immunogenetics Program, Diabetes Research Institute, University of Miami School of Medicine, Miami, 33136, FL, USA Alberto Pugliese & Juan Diez Authors * Alberto Pugliese View author

publications You can also search for this author inPubMed Google Scholar * Juan Diez View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Pugliese, A., Diez, J. Lymphoid organs contain diverse cells expressing self-molecules. _Nat Immunol_ 3, 335–336

(2002). https://doi.org/10.1038/ni0402-335b Download citation * Issue Date: 01 April 2002 * DOI: https://doi.org/10.1038/ni0402-335b SHARE THIS ARTICLE Anyone you share the following link

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