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Evidence for De Novo Expression of Thymic Insulin by Peripheral Bone Marrow-derived Cells.

Carlsén, Maria LU and Cilio, Corrado LU (2008) In Scandinavian Journal of Immunology 68. p.67-74
Abstract
Thymic expression of insulin has been suggested to play a major role in negative selection of autoreactive T cells and tolerance induction against pancreatic beta cells. Furthermore, the expression of insulin in peripheral antigen-presenting cells (APC) has been clearly demonstrated but whether thymic negative selection and tolerance induction also depends on peripheral influx of self-antigens (Ag) remains to be conclusively demonstrated. In this study, we wanted to test whether peripheral influx of insulin expressing cells might contribute to negative selection. In order to address this question, we used mice deficient in the Ins1 and Ins2 genes. Embryonic thymi either deficient in both insulin genes or expressing Ins2 were dissected and... (More)
Thymic expression of insulin has been suggested to play a major role in negative selection of autoreactive T cells and tolerance induction against pancreatic beta cells. Furthermore, the expression of insulin in peripheral antigen-presenting cells (APC) has been clearly demonstrated but whether thymic negative selection and tolerance induction also depends on peripheral influx of self-antigens (Ag) remains to be conclusively demonstrated. In this study, we wanted to test whether peripheral influx of insulin expressing cells might contribute to negative selection. In order to address this question, we used mice deficient in the Ins1 and Ins2 genes. Embryonic thymi either deficient in both insulin genes or expressing Ins2 were dissected and transplanted under the kidney capsule of athymic nude mice recipients. After indicated time points, grafted thymi were removed and analysed for insulin re-expression and for the emergence of autoreactive T cells. The analysis revealed a re-expression of Ins2 in grafted insulin deficient thymi suggesting that self-Ag expression in the thymus is not only intrinsically regulated but peripheral influx of APC capable of expressing insulin might contribute to thymic selection and tolerance induction. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Immunology
volume
68
pages
67 - 74
publisher
Wiley-Blackwell
external identifiers
  • WOS:000256447300007
  • PMID:18482204
  • Scopus:44849126367
ISSN
1365-3083
DOI
10.1111/j.1365-3083.2008.02121.x
language
English
LU publication?
yes
id
0e9ff111-b29d-4f42-a23f-d3333d5e7d06 (old id 1154094)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18482204?dopt=Abstract
date added to LUP
2008-06-05 09:16:27
date last changed
2016-10-13 04:31:27
@misc{0e9ff111-b29d-4f42-a23f-d3333d5e7d06,
  abstract     = {Thymic expression of insulin has been suggested to play a major role in negative selection of autoreactive T cells and tolerance induction against pancreatic beta cells. Furthermore, the expression of insulin in peripheral antigen-presenting cells (APC) has been clearly demonstrated but whether thymic negative selection and tolerance induction also depends on peripheral influx of self-antigens (Ag) remains to be conclusively demonstrated. In this study, we wanted to test whether peripheral influx of insulin expressing cells might contribute to negative selection. In order to address this question, we used mice deficient in the Ins1 and Ins2 genes. Embryonic thymi either deficient in both insulin genes or expressing Ins2 were dissected and transplanted under the kidney capsule of athymic nude mice recipients. After indicated time points, grafted thymi were removed and analysed for insulin re-expression and for the emergence of autoreactive T cells. The analysis revealed a re-expression of Ins2 in grafted insulin deficient thymi suggesting that self-Ag expression in the thymus is not only intrinsically regulated but peripheral influx of APC capable of expressing insulin might contribute to thymic selection and tolerance induction.},
  author       = {Carlsén, Maria and Cilio, Corrado},
  issn         = {1365-3083},
  language     = {eng},
  pages        = {67--74},
  publisher    = {ARRAY(0x95aad28)},
  series       = {Scandinavian Journal of Immunology},
  title        = {Evidence for De Novo Expression of Thymic Insulin by Peripheral Bone Marrow-derived Cells.},
  url          = {http://dx.doi.org/10.1111/j.1365-3083.2008.02121.x},
  volume       = {68},
  year         = {2008},
}