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Publication : Proliferating Transitory T Cells with an Effector-like Transcriptional Signature Emerge from PD-1<sup>+</sup> Stem-like CD8<sup>+</sup> T Cells during Chronic Infection.

First Author  Hudson WH Year  2019
Journal  Immunity Volume  51
Issue  6 Pages  1043-1058.e4
PubMed ID  31810882 Mgi Jnum  J:305827
Mgi Id  MGI:6706564 Doi  10.1016/j.immuni.2019.11.002
Citation  Hudson WH, et al. (2019) Proliferating Transitory T Cells with an Effector-like Transcriptional Signature Emerge from PD-1(+) Stem-like CD8(+) T Cells during Chronic Infection. Immunity 51(6):1043-1058.e4
abstractText  T cell dysfunction is a characteristic feature of chronic viral infection and cancer. Recent studies in chronic lymphocytic choriomeningitis virus (LCMV) infection have defined a PD-1(+) Tcf-1(+) CD8(+) T cell subset capable of self-renewal and differentiation into more terminally differentiated cells that downregulate Tcf-1 and express additional inhibitory molecules such as Tim3. Here, we demonstrated that expression of the glycoprotein CD101 divides this terminally differentiated population into two subsets. Stem-like Tcf-1(+) CD8(+) T cells initially differentiated into a transitory population of CD101(-)Tim3(+) cells that later converted into CD101(+) Tim3(+) cells. Recently generated CD101(-)Tim3(+) cells proliferated in vivo, contributed to viral control, and were marked by an effector-like transcriptional signature including expression of the chemokine receptor CX3CR1, pro-inflammatory cytokines, and granzyme B. PD-1 pathway blockade increased the numbers of CD101(-)Tim3(+) CD8(+) T cells, suggesting that these newly generated transitional cells play a critical role in PD-1-based immunotherapy.
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