Following an RNAseq-based targeted search for novel CD8+ T cell surface markers of exhaustion in the well-studied LCMV system, Hudson et al. found that CD101 expression could be used to distinguish two trajectory-related populations following stimulation of antigen-specific PD-1+Tcf-1+ stem cells. A CD101-Tim3+CX3CR1+ population arose first, characterized by high proliferative capacity, functional capability, and ability to control viral load, followed in 2-4 weeks by CD101+Tim3+CX3CR1- terminally exhausted cells with low proliferative and functional capacity. PD-1 blockade significantly enhanced expansion of the effector CD101- population.
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 down- regulate 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 sub- sets. Stem-like Tcf-1+ CD8+ T cells initially differenti- ated into a transitory population of CD101Tim3+ cells that later converted into CD101+ Tim3+ cells. Recently generated CD101Tim3+ 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 CD101Tim3+ CD8+ T cells, suggesting that these newly generated transitional cells play a critical role in PD-1-based immunotherapy."
Author Info: (1) Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30033, USA (2) Laboratory of Molecular Immunology and the I
Author Info: (1) Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30033, USA (2) Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA (3) Department of Urology, Emory University School of Medicine, Atlanta GA 30033, USA (4) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA USA (5) Lead contact
