Evaluation of the Exhaustion of T -Helper Lymphocytes in Peripheral Blood of Kidney Allograft-Receiving Patients

Abstract

T cell Immunoglobulin and ITIM domain (TIGIT) molecule is an inhibitory helper molecule expressed on T and NK cells, whose main ligand is the CD155 (Polio Virus Receptor) molecule. The signaling of this molecule is a negative regulator of T-lymphocyte function and through the deactivation of active cell signaling and the effect on cell metabolism, it causes exhaustion of immune responses. Considering the importance of the mentioned molecules in tolerance against allografts and also the unknown role of these molecules in human cases of developing tolerance to kidney allografts, the aim of this study is to determine the possible relationship between the expression of the mentioned molecules in peripheral blood T lymphocytes of patients. Transplantation is related to kidney function. Also, the immunological correlation of relative differences observed in kidney allograft acceptance in different recipients was investigated. Materials and Methods: In order to investigate PD-1 and TIGIT markers on TCD4+ and TCD8+ cells, the heparinized blood received from the transplant recipients in the following tubes was stained by 3-color flow cytometry for each of PD-1 and TIGIT markers. Before flow cytometry analysis, cell sediment is destroyed by RBC lysing solution, RBCs of the blood sample are destroyed and read by flow cytometry according to the available controls. The percentage and MFI of PD-1 and TIGIT markers were read on TCD4+ and TCD8+ cells. Serum creatinine and BUN levels of the received samples are measured by commercial calorimetric kits. The relationship between the expression of studied markers and the level of cytokines with the level of creatinine and BUN of the studied patients was determined through a correlation test. Results: A higher percentage of T helper cells expressing PD-1 (CD4+, PD-1+) was observed in the peripheral blood of patients with creatinine levels below 2 (P=0.003); The expression of PD-1 and TIGIT as well as the percentage of CD4+ and TIGIT+ cells had no significant correlation with the serum creatinine level in transplant patients, while the percentage of CD4+ and PD-1+ cells in these patients showed a significant inverse correlation with the creatinine level. (r = -0.59 and P<0.001).