Proliferation control of specific-effector T cells and T-Regulatory cells by Tim-3 and Galectin-9 in Drug-Induced Maculopapular Exanthema

Galectin-9 is a molecule with a wide range of biological activities, including the control of some immunological processes. The inability to produce enough amount of Galectin-9 and/or an incorrect interaction with its receptor Tim-3, could be responsible for the uncontrolled increase of Th1 cells as happen in Drug-Induced Maculopapular Exanthema (DIMPE). Our aim was to analyze the role of Galectin-9 and Tim-3 in the proliferation of specific-effector T cells and Tregs in patients with DIMPE. Peripheral blood mononuclear cells (PBMCs) were isolated from 18 patients with DIMPE and 10 controls. PBMCs were cultured with the culprit drug in presence of carboxyfluoresceinsuccinimidyl ester (CFSE) to analyze the proliferation of Th1 (CD4+CXCR3+), Tim-3+Th1 (CD4+CXCR3+Tim-3+), and Tregs (CD4+CD25highFoxp3+) by flow cytometry. Exogenous Galectin-9 was added, as well as antibodies aTim-3 to enhance or block the interaction respectively. Results were represented as proliferation index (PI). Higher PI was found when Th1, Tim-3+Th1 and Tregs cells from allergic patients with DIMPE were cultured with the culprit drug compared to controls (p=0.008, p=0.012, p=0.002 respectively). The addition of antibodies aTim-3 did not reduce the proliferation of any population. On the contrary, the addition of Galectin-9 reduced the proliferation of Th1 (p=0.025) and Tim-3+Th1 cells (p=0.026), whereas increased the PI of Tregs (p<0.001). Galectin-9 has an important dual effect: its addition reduces the proliferation of specific-effector cells, whereas promotes the proliferation of Tregs in DIMPE patients. These data suggest that Galectin-9 could represent a therapeutical candidate able to control the disease.