Figure 2.

Differentiation program of CD8 T cells during chronic HCV infection. Naïve-like T cells expresses the transcription factor TCF1 and the lymphocyte homing and adhesion molecule receptors CD62L and CCR7 and, the positive co-stimulatory molecule CD28. After T cell priming, the naïve pool differentiates into stem-like precursor and precursor subset. These pools maintain TCF1 expression, are CD127 positive, display a catabolic mitochondrial metabolism and have self-renewal potential. The stem-like precursor subset expresses the chemokine receptor CXCR5 and are found in primary lymphoid organs. The precursor pool loses CXCR5 and can be found in the periphery, giving rise to the effector-like transitory subset, but also can dedifferentiate into the stem-like precursor pool. The progeny subset is comprised by the effector-like transitory cells, which expresses the chemokine receptor CX3CR1 and loss TCF1 expression. Finally, this pool differentiates into the late dysfunctional subset characterized by loss of functionality and the expression of several negative immune checkpoints.