Figure 1.

.#Therapeutic strategies to restore the functional T cell immune response. Activation of CD8+ T cells requires MHC-I presentation of antigenic peptide to TCR and co-stimulatory (such as CD80/CD86-CD28 engagement) and cytokine signaling. Excessive TCR stimulation induces the expression of co-inhibitory receptors on T cells. Activation of co-inhibitory receptors induces inhibitory gene expression and functional exhaustion of T cells. Mitochondrial dysfunction and extensive reprogramming of cell metabolism also contribute to the functional exhaustion of T cells. Four therapeutics strategies for restoration of exhausted CD8+ T cell are proposed.