Evaluation of in vivo T cell kinetics: use of heavy isotope labelling in type 1 diabetes. (18th April 2013)

• Record Type: Journal Article
• Authors: Bollyky, J. B.; Long, S. A.; Fitch, M.; Bollyky, P. L.; Rieck, M.; Rogers, R.; Samuels, P. L.; Sanda, S.; Buckner, J. H.; Hellerstein, M. K.; Greenbaum, C. J.
• Is Part Of: Clinical and experimental immunology. Volume 172:Number 3(2013:Jun.)
• Page Start: 363
• Page End: 374
• Publication Date: 2013-04-18
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12064
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>CD4<sup>+</sup> memory cell development is dependent upon T cell receptor (TCR) signal strength, antigen dose and the cytokine milieu, all of which are altered in type 1 diabetes (T1D). We hypothesized that CD4<sup>+</sup> T cell turnover would be greater in type 1 diabetes subjects compared to controls. <italic>In vitro</italic> studies of T cell function are unable to evaluate dynamic aspects of immune cell homoeostasis. Therefore, we used deuterium oxide (<sup>2</sup>H<sub>2</sub>O) to assess <italic>in vivo</italic> turnover of CD4<sup>+</sup> T cell subsets in T1D (<italic>n</italic> = 10) and control subjects (<italic>n</italic> = 10). Serial samples of naive, memory and regulatory (T<sub>reg</sub>) CD4<sup>+</sup> T cell subsets were collected and enrichment of deoxyribose was determined by gas chromatography–mass spectrometry (GC–MS). Quantification of T cell turnover was performed using mathematical models to estimate fractional enrichment (f, <italic>n</italic> = 20), turnover rate (k, <italic>n</italic> = 20), proliferation (p, <italic>n</italic> = 10) and disappearance (d*, <italic>n</italic> = 10). Although turnover of T<sub>regs</sub> was greater than memory and naive cells in both controls and T1D subjects, no differences were seen between T1D and controls in T<sub>reg</sub> or naive kinetics. However, turnover of CD4<sup>+</sup> memory T cells was faster in those with T1D compared to control subjects. Measurement and modelling of incorporated deuterium is useful for evaluating the <italic>in vivo</italic> kinetics of immune cells in T1D and could be incorporated into studies of the natural history of disease or clinical trials designed to alter the disease course. The enhanced CD4<sup>+</sup> memory T cell turnover in T1D may be important in understanding the pathophysiology and potential treatments of autoimmune diabetes.</p> </abstract>