Elevated Expression of Tim-3 and PD-1 Immune Checkpoint Receptors on T-CD4+ Lymphocytes of Patients with Asthma

Asthma is a chronic disorder of the airways characterized by reversible airflow obstruction, inflammation and bronchial hyperresponsiveness. Different immune cells and molecules have been attributed to involve in pathogenesis of asthma. In the current case-control study, the expression of T cell Ig and mucin domain-containing molecule-3 (Tim-3) and programmed death-1 (PD-1) was studied on CD4+ T cells of patients with asthma and normal controls. The frequency of Tim-3(+)/PD-1(+)/CD4(-) T cells was determined by a three color flow cytometry method in 37 patients with asthma and 32 healthy controls. To evaluate the Th1/Th2 ratio, peripheral blood mononuclear cells were isolated from all samples and stimulated with phorbol 12- myristate 13- acetate (PMA)/ionomycin for 18 h. IFN-gamma and Interleukin-4 (IL-4) were measured in culture supernatants by ELISA. Serum total immunoglobulin E (IgE) was also measured in all samples. Significant increase in percentage and absolute count of Tim-3(+)/PD-1(+)/CD4(+), Tim-3(+)/CD4(+) and PD-1(+)/CD4(+) T cells was found in asthmatic patients compared to healthy controls (p=0.02, p<0.0001 and p=0.01, respectively). The IFN-gamma/IL-4 ratio (Th1/Th2 ratio) was significantly higher in healthy controls than that of asthmatic patients (p=0.029). Our data regarding the increased expression of PD-1 and Tim-3 on CD4(+) T cells of patients with asthma suggest the potential roles of these immune checkpoint receptors in immune dys-regulation of asthma.