Senescent profile of angiogenic T cells from systemic lupus erythematosus patients

Abstract

The chronic inflammatory environment associated with systemic lupus erythematosus can lead to an accelerated immunosenescence responsible for the endothelial damage and increased cardiovascular risk observed in these patients. The present study analyzed two populations with opposite effects on vascular endothelium, angiogenic T cells and the senescent CD4(+)CD28(null) subset, in 84 systemic lupus erythematosus patients and 46 healthy controls. Also, 48 rheumatoid arthritis patients and 72 individuals with traditional cardiovascular risk factors participated as disease controls. Phenotypic characterization of CD28(+) and CD28(null) cells was performed by analyzing markers of senescence (CCR7, CD27, CD57) and cytotoxicity (CD56, perforin, granzyme B, IFN-γ). IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17A, IFN-α, IFN-γ, TNF-α, B lymphocyte stimulator, and GM-CSF serum levels were analyzed in systemic lupus erythematosus patients and healthy controls. CD4(+)CD28(null) cells were notably increased in the systemic lupus erythematosus patients and disease controls compared with healthy controls. In contrast, angiogenic T cells were only reduced in the disease controls (those with rheumatoid arthritis or traditional cardiovascular risk factors). Nevertheless, an anomalous presence of CD28(null)-angiogenic T cells, with cytotoxic and senescent characteristics, was noted in systemic lupus erythematosus patients in association with anti-dsDNA titer, anti-SSA/Ro antibodies and circulating TNF-α, IL-8, IFN-α, and B lymphocyte stimulator amounts. This subset was also detected in those with traditional cardiovascular risk factors but not in the rheumatoid arthritis patients. In contrast, CD28(+)-angiogenic T cells were reduced in the systemic lupus erythematosus patients with cardiovascular disorders. In conclusion, CD28 expression must be used to redefine the angiogenic T cell population, because in pathologic conditions, a senescent CD28(null)-angiogenic T cell subset with inflammatory, rather than protective, effects could be present.

Older men display elevated levels of senescence-associated exercise-responsive CD28nullangiogenic T cells compared with younger men

“…In addition, these CD28 null T ANG cells also co‐expressed other differentiation markers, including CD56, perforin, granzyme B, and IFN‐ γ , as well as CD57 which support the theory that CD28 null T ANG cells display a senescent profile (Lopez et al. ). CD28 + T ANG cells did not express these markers; however, they did express CD27, a T‐cell differentiation marker (Hintzen et al.…”

“…We report that older adults display reduced number of circulating T ANG cells (including CD4 + and CD8 + subsets), but also display increased proportion of T ANG cells lacking CD28 expression which is associated with a senescent T ANG profile (Lopez et al. ). Our results also show that older adults display a blunted responsiveness of T ANG cells to moderate intensity exercise.…”

“…Recently, CD28 null T ANG cells were shown to be reduced in individuals with elevated cardiovascular risk factors and in those with SLE than healthy age‐matched controls (Lopez et al. ). These cells were also characterized as expressing granzyme B, perforin, IFN‐ γ , and markers, such as CD57, CCR7, and CD56, indicative of a senescent and cytotoxic profile.…”

“…In a recent study, CD28 null T ANG cells were significantly elevated in patients with cardiovascular risk factors and those with systemic lupus erythematosus (SLE) compared with healthy controls (Lopez et al. ). These cells were associated with increased circulating levels of TNF‐ α , IL‐8, IFN‐ α , and IL‐10, suggesting a role in promoting inflammatory conditions.…”

DUSP23 is over-expressed and linked to the expression of DNMTs in CD4+ T cells from systemic lupus erythematosus patients

“…Another phosphatase which also seems to inhibit signalling through the ERK and JNK pathways (and consequently leads to a decrease in DNMT1 and DNMT3A levels) is protein phosphatase 5 (PP5). CD4 + CD28 – T cells express high levels of PP5, and this cell subset is increased notably in SLE patients . Together, these observations indicate that the enhanced expression of particular phosphatases may impair these signalling pathways and may contribute to human lupus by decreasing DNA methylation, which eventually causes gene dysregulation and autoreactivity.…”