IL-7 Receptor Alpha Chain Expression Identifies Human CD8+ Memory T Cell Subsets with Distinct Gene Expression Profiles and TCR Repertoire Compositions

Abstract

Abstract Heterogeneity of CD8 T cell play crucial roles in cancer patients and reveals the co-evolution between tumor and immunity. While CD127 expression identifies memory precursor cells during acute infections, the role of CD127 expression in defining memory T cell heterogeneity is not investigated. Here, we analyzed the Vβ-CDR3 usage of human effector memory TEM and TEMRA cells accompanied by functional and gene expression patterns based on surface CD127 expression. We found that, CD127hi subsets are associated with higher level of TCR diversity regardless of their TEM or TEMRA phenotype. CD127lo populations are presented with relatively low TCR repertoire diversity. Moreover, there is a high correlation between CD127hi and CD127lo populations which imply possible differentiation tract between CD127hi and CD127lo T cells, but not between TEM and TEMRA cells. On the other hand, both TEM and TEMRA CD127lo populations showed higher expression of effector genes including perforin, granzyme B, granzyme H, and pan-inhibitory killer immunoglobulin-like receptors, exhibited lower phenotype plasticity upon TCR activation and cytokine-driven proliferation, when compared to their CD127hi counterparts. In other words, depending on the expression of CD127, T cells from either TEM or TEMRA are similar in their gene expression and functionality patterns. These results provide the first evidence that T cell repertoire and gene expression signature can be uncoupled based on distinct CD127-dependent phenotype expression patterns but are delicately balanced in the memory T cell pool.