Immunome Research
Open Access

Abstract

T Cell Immunoglobulin Mucin-3 (TIM-3) Expression on Peripheral Blood Lymphocytes in Chronic Hepatitis Virus C Infection

Hydi Ahmed, Sahar Abo-Elfotoh Abdel Wahed, Zinab Mohammed Mahmoud Diab and Abdelhady Ragab Abdel-Gawad

Introduction: T cell Immunoglobulin Mucin-3 (TIM-3) TIM-3 acts as a negative regulator of (T helper-1)Th1/ (T Cytotoxic-1)Tc1 cell function by triggering cell death upon interaction with its ligand Galectin-9, a feature observed in chronic viral diseases.

Objective: To demonstrate the level of expression of TIM-3 on Peripheral Blood Mononuclear cells (PBCs) in cases of chronic HCV as a number of emerging molecules and pathways have been implicated in mediating the Tcell exhaustion characteristic of chronic viral infection. Patients and Methods: This study included 90 subjects, divided up as follows: Group 1 (35 patients) included HCV antibody positive with normal liver functions (Compensated), Group 2 (35 patients) comprised HCV antibody positive patients with abnormal liver functions (decompensated), and controls (Group 3) involved 20 apparently healthy persons (HCV antibody negative persons). The following laboratory investigations were performed for all participants in the 3 groups: Complete Blood Count (CBC), Blood Chemistry (liver functions), Special investigations (Flowcytometric study, and PCR for HCV RNA).

Results: Comparing the control, compensated and decompensated groups regarding lymphocytic counts, ratios of TIM-3 positive cells within CD4, CD8, CD14 and CD56 cells in the three groups. Ratio of CD4 cells was higher in the compensated and control groups, than in the decompensated group, with non-significant difference. CD8 cells were maximum in the decompensated groups and minimum in the compensated group, with a significant p value. CD14 cells were maximum in the compensated group, followed by decompensated and minimum in the control group, again with a significant difference. CD56 showed non-significant differences between the three groups. A steady increase in the percentage of TIM +ve CD4, CD8, CD14 and CD 56 cells, with maximum percentages among the decompensated liver disease group, and least percentage among the control group was seen. The differences were significant regarding CD8 and CD56 and highly significant regarding CD4 and CD14 cells.

Conclusions: Accumulation of TIM-3+ T cells is associated with functional impairment, and consequently with development of persistent HCV. The present study provides a basis for improving current therapies by simultaneous blockade of multiple inhibitory pathways that could result in additive efficacy without excessive toxicity. These findings have implications for the development of novel immunotherapeutic approaches to this common viral infection.