Effect of selected non-steroidal anti-inflammatory drugs on activation-induced CD25 expression on murine CD4+ and CD8+ T cells: an in vitro study

Abstract

The main aim of this study has been to determine the effect of selected non-steroidal anti-inflammatory drugs (NSAIDs) – depending on their selectivity to cyclooxygenase (COX) 1 and 2 – on the activation-induced CD25 expression on CD4+ and CD8+ T cells. Lymphocytes obtained from lymph nodes of mice were treated with acetylsalicylic acid (ASA; a preferential COX-1 inhibitor), ketoprofen (KET; a non-selective COX inhibitor) and robenacoxib (ROB; a selective COX-2 inhibitor) in concentrations reflecting their plasma levels achieved in vivo at therapeutic doses and in ten-fold lower concentrations. The cells were activated with concanavalin A. In contrast to KET and ROB, ASA had no effect on the activation-induced CD25 expression on CD4+ and CD8+ T cells, nor did it affect the counts of CD4+ and CD8+ activated effector (aTeff) and resting (Trest) T cells. Both KET and ROB caused a depletion of CD8+ aTeff cells, and additionally KET induced a loss of CD8+ Trest cells. Moreover, ROB, but not the other drugs, reduced the activation-induced CD25 expression on CD4+ T cells. This suggests that non-selective COX inhibitors and selective COX-2 inhibitors may weaken the effector T cell response by producing a negative effect on the count of aTeff cells. Furthermore, the results seem to imply that ASA and KET have certain potential to induce Foxp3 expression in CD25+CD8+ and CD25+CD4+ T cells, respectively. However, all the observed changes were very weakly manifested and therefore it is not certain whether they have clinical importance, despite the statistical significance determined.

Prostaglandin E2 directly inhibits the conversion of inducible regulatory T cells through EP2 and EP4 receptors via antagonizing TGF‐β signalling

“…Foxp3, IL-10) expression from both mouse and human effector T cells through direct actions on T cells via EP2 and/or EP4 receptors [32,33,[61][62][63][64]. In agreement with these reports, blocking PG biosynthesis including PGE 2 production by NSAIDs or blocking PGE 2 signalling by an EP4 selective antagonist enhanced Foxp3 expression and iTreg induction, and therefore ameliorated T cell-mediated tissue inflammation [32,[65][66][67]. Moreover, we have recently found that PGE 2 inhibits Treg cell expansion or accumulation in the intestine through T cell-independent but microbiotadependent mechanisms [35].…”

Investigation of Early Supplementation of Nucleotides on the Intestinal Maturation of Weaned Piglets

“…PTI is a gene for which there is not a true homolog in humans, coding for a pancreatic trypsin inhibitor, long known for pigs [ 38 ]. In the pancreas, it has a protective action, while in the blood it could have relevance as an antifibrinolytic factor on the homology of the molecule of bovine origin [ 39 ]. Regulation of the activation of PTI has not been studied previously, even though there is increasing interest in medicine regarding this kind of protein.…”

TET 2 promotes anti‐tumor immunity by governing G‐ MDSC s and CD 8 + T‐cell numbers

“…Finally, we also examined CD39 + (T-cell exhaustion marker) (Canale et al, 2018) and CD25 + (T-cell activation marker) immune cells (Gregorczyk & Maslanka, 2019) by flow cytometry analysis. After treatment with anti-IL-6, CD39 + immune cells in Tet2 À/À mice decreased to WT levels, while CD25 + immune cells in Tet2 À/À mice increased to WT levels ( Fig EV5D-G).…”