КОИНГИБИРУЮЩИЕ МОЛЕКУЛЫ В НОРМЕ И ПРИ ПАТОЛОГИИ. КОНТРОЛЬНЫЕ ТОЧКИ (CHECKPOINT) ИММУНОРЕГУЛЯЦИИ. Часть 1. Роль коингибирующих молекул в нормальном иммунном ответе, при аллергии и аутоиммунных заболеваниях

The differentiation and protective capacity of antigen-specific T-cells are regulated by both positive and negative signals. Molecules of the B 7/CD 28 family are very important for regulating T-cell activation and peripheral tolerance. In particular, PD-1, CTLA-4 and other co-inhibitory molecules play an active role in dampening of excessive immune activation which is critical for successful clearance of a pathogen without harm to the host. These co-inhibitory molecules (immunological checkpoints) are essential for inducible Treg differentiation and function. On the other hand, overexpression of co-inhibitory molecules can lead to T-cell exhaustion, an adaptive property that occurs in T-cells due to persistent systemic antigen exposure. Exhausted T-cells are described as effector T-cells with decreased cytokine expression and effector function. Here, we review a critical role of co-inhibitory molecules which they play in immunopathogenesis of four immunological syndromes: allergy, autoimmune diseases, chronic infection, and cancer. Reversal of exhausted T-cells by blocking co-inhibitory pathways has become an important area due to its therapeutic applications in oncology and chronic viral infections.