Should we consider blocking the inhibitory immune checkpoint molecules for treating T cell exhaustion in sepsis?

Excerpt

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection [1]. These dysregulated host responses involve the immune system and other organ systems, manifesting as organ dysfunction [1]. The dysregulated immune responses in sepsis affect both the innate and the adaptive immune systems. There is immune activation alongside functional impairment of innate and adaptive immune cells [2]. One aspect of adaptive immune system changes that contributes towards sepsis-related immunosuppression is impaired lymphocyte function, alongside accelerated lymphocyte loss [2]. The reason being, in health, activated CD4+ helper T cells secrete an array of cytokines and chemokines to recruit innate immune cells to sites of infection, enhance their microbicidal activity, help B lymphocyte class switch to make antibodies and generate long-lived lymphocyte memory [3]. Another unique property of CD4+ helper T cells is that they can initiate a cellular programme to polarise towards a particular subset, based on the danger signals they sense [4]. In sepsis, there is a polarisation towards T helper-2 subsets [5]. …