Lymphoid tissue residency: A key to understand Tcf-1(+)PD-1(+) T cells

During chronic antigen exposure, a subset of exhausted CD8(+) T cells differentiate into stem cell-like or progenitor-like T cells expressing both transcription factor Tcf-1 (T cell factor-1) and co-inhibitory receptor PD-1. These Tcf-1(+) stem-like or progenitor exhausted T cells represent the key target for immunotherapies. Deeper understanding of the biology of Tcf-1(+)PD-1(+) CD8(+) T cells will lead to rational design of future immunotherapies. Here, we summarize recent findings about the migratory and resident behavior of Tcf-1(+) T cells. Specifically, we will focus on TGF-β-dependent lymphoid tissue residency program of Tcf-1(+) T cells, which may represent a key to understanding the differentiation and maintenance of Tcf-1(+) stem-like CD8(+) T cells during persistent antigen stimulation.