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Regulatory T cell-associated activity in photopheresis-induced immune tolerance in recent onset type 1 diabetes children.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2008 Aug; Vol. 153 (2), pp. 174-81. Date of Electronic Publication: 2008 Jun 28. - Publication Year :
- 2008
-
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 < 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.
- Subjects :
- Adolescent
Antigens, CD blood
Antigens, CD genetics
Biomarkers
CTLA-4 Antigen
Case-Control Studies
Child
Female
Forkhead Transcription Factors genetics
Gene Expression Regulation
Glutamate Decarboxylase pharmacology
Humans
Immune Tolerance
Lymphocyte Activation
Male
Phytohemagglutinins pharmacology
RNA, Messenger analysis
Reverse Transcriptase Polymerase Chain Reaction methods
Statistics, Nonparametric
Transforming Growth Factor beta genetics
Diabetes Mellitus, Type 1 immunology
Diabetes Mellitus, Type 1 therapy
Photopheresis
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2249
- Volume :
- 153
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 18549445
- Full Text :
- https://doi.org/10.1111/j.1365-2249.2008.03625.x