Decreased numbers of signal-joint T cell receptor excision circle-containing CD4+ and CD8+ cells in systemic lupus erythematosus patients

Abstract

Systemic lupus erythematosus (SLE) patients have a decreased number of peripheral blood T cells containing signal-joint T cell receptor excision circles (Sj TRECs), which are considered an indicator of thymic output. The objective of this study was to investigate the mechanism of the decrease in such T cells. Peripheral blood T cells from SLE patients were classified into CD4+ and CD8+ cells. Sj TREC levels were measured by real-time PCR. Telomerase activity was determined by the telomeric repeat amplification protocol assay. The numbers of Sj TREC containing CD4+ and CD8+ cells were lower in the peripheral blood of SLE patients than in the controls. A correlation was found between the numbers of Sj TREC-positive CD4+ and CD8+ cells. The level of TRECs is influenced by an increase in cell division. To examine this increase, telomerase activity as an indicator of cell division was measured simultaneously; however, there was no correlation between the Sj TREC level and telomerase activity. These results suggest that decreased thymic output occurs in SLE patients.

Reduced T-Cell Thymic Export Reflected by sj-TREC in Patients with Coronary Artery Disease

“…In this study, telomerase was not measured, and the proportion of proliferating T cells was so rare that its increase could not mediate such a marked reduction in sj-TREC copy number in the periphery. Therefore, it is commonly recognized that division and differentiation do not affect the total sj-TREC level in T lymphocytes 10,53) , and the reduction of sj-TREC concentration observed mainly results from decreased thymic output 41) . The thymus is the central lymphoid organ for the production of naïve T cells, which lack the capability of expressing pro-inflammatory cytokines, such as TNF- 50) .…”

“…To exclude the possibility that T-cell proliferative turnover may account for decreased copy number of sj-TRECs, T-cell telomere length, a known indicator of increased cell division 10,11) , was assessed and found not to differ among study groups. Although both decreased sj-TREC level and increased telomerase activity were observed in SLE patients 10) , studies reported no significant correlation between sj-TREC level and telomerase activity as an indicator of increased lymphocytes division 10,51) . Moreover, because telomer- Relative T/S ratios were measured by monochrome multiplex quantitative PCR method (MMQPCR) with albumin used as the single copy gene.…”

“…Reduction of recent thymic emigration (RTE) and consequently lopsided T cell homeostasis can trigger some kind of autoimmune diseases, such as rheumatoid arthritis (RA), in experimental models [9][10][11][12] . In previous studies, investigators assessed output naïve T cells to determine whether T cell homeostasis regulated by continuous thymic export was impaired in patients with CAD 13) .…”

Increased concentration of T‐cell receptor rearrangement excision circles (TREC) in peripheral blood in Graves' disease

“…Recently, a number of studies used TREC concentration measurements to assess thymic function in autoimmune diseases such as rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), systemic lupus erythematosus (SLE) and multiple sclerosis (MS) . It has been consistently found that among the patients, there was a decrease of thymic output when compared to age‐matched controls . The only disease which apparently did not follow this pattern being associated with increased thymic activity was myasthenia gravis (MG) and type 1 diabetes mellitus (T1DM).…”

Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1+CXCR5−/dim B-helper T cell induction

“…Indeed, LIP is reported to be involved in the pathogenesis of human autoimmune diseases such as SLE12, rheumatoid arthritis6, and multiple sclerosis13, and has been revealed as a direct cause of type-1 diabetes in non-obese diabetes (NOD) mice14 and arthritis in K/BxN mice15. A classical manipulative LIP-induced autoimmune murine model is neonatal thymectomized mice, which develop multiple organ-specific inflammations including gastritis, thyroiditis, oophoritis, sialoadenitis, and nephritis, with the production of organ-specific antibodies, such as anti-parietal cell antibody1617.…”