CD 127- and FoxP3+ expression on CD25+CD4+ T regulatory cells upon specific diabetogeneic stimulation in high-risk relatives of type 1 diabetes mellitus patients.
Abnormalities in CD4+CD25+ regulatory T cells (Treg) may contribute to type 1 diabetes (T1D) development. First-degree relatives of T1D patients are at increased risk especially when they carry certain HLA II haplotypes. Using two novel markers of CD4+CD25+ Treg (CD127- and FoxP3+ respectively), we evaluated number and function of Treg after specific stimulation with diabetogeneic autoantigens in 11 high-risk (according to HLA-linked risk) relatives of T1D patients and 14 age-matched healthy controls using a cytokine secretion assay based on interferon-gamma (IFN-gamma) production. High-risk relatives of T1D patients had significantly lower pre- and post-stimulatory number of CD127- Treg than that of healthy controls (P < 0.05). Labelling Treg with FoxP3+ demonstrated similar trend but did not reach statistical significance. Although the stimulation with diabetogenic autoantigens did not lead to a significant change in number of Treg in both groups, the defective function of Treg was performed by significantly higher activation of diabetogeneic T cells in high-risk relatives of T1D patients compared to healthy controls (P < or = 0.02). Individuals at increased HLA-associated genetic risk for T1D showed defects in Treg.
Vrabelova
Z
Z
Department of Pediatrics, University Hospital Motol, Prague, Czech Republic. zuzanavr@email.cz
Hrotekova
Z
Z
Hladikova
Z
Z
Bohmova
K
K
Stechova
K
K
Michalek
J
J
D000293:Adolescent; D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D018655:Lymphocyte Count; D008297:Male; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit