Two distinct subpopulations of human stem-like memory T cells exhibit complementary roles in self-renewal and clonal longevity
Fig 3
CD8+ TN, CD95int TSCM, CD95hi TSCM, TCM, TEM and TEMRA populations were sorted. Cells were either unstimulated or stimulated with αCD3αCD28. RNA was extracted and sequenced. (A) PCA representation of the most variable genes showed that, for unstimulated cells, CD95int TSCM clustered near TN, whereas CD95hi TSCM clustered with TCM. Upon stimulation these four populations separated with both TSCM subpopulations distinct from each other and from TN and TCM cells. (B) Gene set enrichment analysis of genes differentially expressed between unstimulated CD95int TSCM and unstimulated CD95hi TSCM found, transcriptionally CD95int TSCM were closer to naïve CD4 and CD8+ T cells while CD95hi TSCM were correspondingly closer to various memory populations (i.e., genes that were down in naïve v memory CD4, naïve v effector memory CD4 and naïve v PD1 hi CD8 were also down in CD95int TSCM). (C) The same analysis for of genes differentially expressed between stimulated CD95int TSCM and stimulated CD95hi TSCM was harder to interpret. The only T cell pathway (GSE21360, PRIMARY VS QUATERNARY MEMORY CD8 TCELL UP) implies that genes upregulated in CD95hi TSCM are enriched in genes upregulated in memory CD8 T cells following multiple antigen challenge whereas genes upregulated in CD95int TSCM are associated with memory CD8+ T cells following primary antigen challenge.