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Regulatory T cell-associated activity in photopheresis-induced immune tolerance in recent onset type 1 diabetes children

Jonson, C. -O.; Pihl, M.; Bolmeson, Caroline LU ; Cilio, Corrado LU ; Ludvigsson, J. and Faresjo, M. (2008) In Clinical and Experimental Immunology 153(2). p.174-181
Abstract
Extracorporeal photochemotherapy (ECP) has demonstrated immunological effects. The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-beta are associated with regulatory T cell activity. The aim of the study was to evaluate the regulatory T cell-associated effect of ECP in recent onset type 1 diabetic (T1D) children. Children (n = 20) with T1D received photopheresis 8-methoxypsoralen + ECP or placebo + shampheresis. Peripheral blood mononuclear cells (PBMC) collected pretreatment (day 1) and post-treatment (day 90) were stimulated with phytohaemagglutinin (PHA) and T1D-associated glutamic acid decarboxylase 65 (GAD(65)) peptide a.a. 247-279. CTLA-4,... (More)
Extracorporeal photochemotherapy (ECP) has demonstrated immunological effects. The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-beta are associated with regulatory T cell activity. The aim of the study was to evaluate the regulatory T cell-associated effect of ECP in recent onset type 1 diabetic (T1D) children. Children (n = 20) with T1D received photopheresis 8-methoxypsoralen + ECP or placebo + shampheresis. Peripheral blood mononuclear cells (PBMC) collected pretreatment (day 1) and post-treatment (day 90) were stimulated with phytohaemagglutinin (PHA) and T1D-associated glutamic acid decarboxylase 65 (GAD(65)) peptide a.a. 247-279. CTLA-4, sCTLA-4, FoxP3 and TGF-beta mRNA transcription was quantified. Photopheresis-treated individuals' relative mRNA expression was generally maintained during the course of the study. Placebo individuals increased in spontaneous CTLA-4 mRNA (P < 0.05) but decreased in expression after stimulation with GAD(65)-peptide (P < 0.05) and PHA (P < 0.05). Spontaneous TGF-beta (P < 0.05) increased whereas PHA- (P < 0.01) and GAD(65)-peptide (P < 0.01)-induced TGF-beta expression decreased in the placebo group, whereas it was maintained in the treated group. Without intervention, expression of CTLA-4 and TGF-beta, stimulated with PHA and GAD(65) peptide, decreased with time, with a parallel reduction of GAD(65)-peptide and PHA-stimulated TGF-beta expression. These parameters were counteracted by ECP. In conclusion, our results indicate that ECP maintains regulatory T cell-associated activity in recent-onset T1D. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
T1D, T-reg, children, extracorporeal photochemotherapy
in
Clinical and Experimental Immunology
volume
153
issue
2
pages
174 - 181
publisher
British Society for Immunology
external identifiers
  • wos:000257550500003
  • scopus:47249122232
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2008.03625.x
language
English
LU publication?
yes
id
c317e6d3-97c5-4857-8afa-77cb343fd47c (old id 1255081)
date added to LUP
2008-10-17 14:14:07
date last changed
2017-01-01 04:48:49
@article{c317e6d3-97c5-4857-8afa-77cb343fd47c,
  abstract     = {Extracorporeal photochemotherapy (ECP) has demonstrated immunological effects. The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-beta are associated with regulatory T cell activity. The aim of the study was to evaluate the regulatory T cell-associated effect of ECP in recent onset type 1 diabetic (T1D) children. Children (n = 20) with T1D received photopheresis 8-methoxypsoralen + ECP or placebo + shampheresis. Peripheral blood mononuclear cells (PBMC) collected pretreatment (day 1) and post-treatment (day 90) were stimulated with phytohaemagglutinin (PHA) and T1D-associated glutamic acid decarboxylase 65 (GAD(65)) peptide a.a. 247-279. CTLA-4, sCTLA-4, FoxP3 and TGF-beta mRNA transcription was quantified. Photopheresis-treated individuals' relative mRNA expression was generally maintained during the course of the study. Placebo individuals increased in spontaneous CTLA-4 mRNA (P &lt; 0.05) but decreased in expression after stimulation with GAD(65)-peptide (P &lt; 0.05) and PHA (P &lt; 0.05). Spontaneous TGF-beta (P &lt; 0.05) increased whereas PHA- (P &lt; 0.01) and GAD(65)-peptide (P &lt; 0.01)-induced TGF-beta expression decreased in the placebo group, whereas it was maintained in the treated group. Without intervention, expression of CTLA-4 and TGF-beta, stimulated with PHA and GAD(65) peptide, decreased with time, with a parallel reduction of GAD(65)-peptide and PHA-stimulated TGF-beta expression. These parameters were counteracted by ECP. In conclusion, our results indicate that ECP maintains regulatory T cell-associated activity in recent-onset T1D.},
  author       = {Jonson, C. -O. and Pihl, M. and Bolmeson, Caroline and Cilio, Corrado and Ludvigsson, J. and Faresjo, M.},
  issn         = {0009-9104},
  keyword      = {T1D,T-reg,children,extracorporeal photochemotherapy},
  language     = {eng},
  number       = {2},
  pages        = {174--181},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Regulatory T cell-associated activity in photopheresis-induced immune tolerance in recent onset type 1 diabetes children},
  url          = {http://dx.doi.org/10.1111/j.1365-2249.2008.03625.x},
  volume       = {153},
  year         = {2008},
}