Model of the adaptive immune response system against HCV infection reveals potential immunomodulatory agents for combination therapy.

A regulated immune system employs multiple cell types, diverse variety of cytokines and interacting signalling networks against infections. Systems biology offers a promising solution to model and simulate such large populations of interacting components of immune systems holistically. This study focuses on the distinct components of the adaptive immune system and analysis, both individually and in association with HCV infection. The effective and failed adaptive immune response models have been developed followed by interventions/perturbations of various treatment strategies to get better assessment of the treatment responses under varying stimuli. Based on the model predictions, the NK cells, T regulatory cells, IL-10, IL-21, IL-12, IL-2 entities are found to be the most critical determinants of treatment response. The proposed potential immunomodulatory therapeutic interventions include IL-21 treatment, blocking of inhibitory receptors on T-cells and exogenous anti-IL-10 antibody treatment. The relative results showed that these interventions have differential effect on the expression levels of cellular and cytokines entities of the immune response. Notably, IL-21 enhances the expression of NK cells, Cytotoxic T lymphocytes and CD4+ T cells and hence restore the host immune potential. The models presented here provide a starting point for cost-effective analysis and more comprehensive modeling of biological phenomenon.