A New Subset of Human Naive CD8+ T Cells Defined by Low Expression of IL-7Rα

Abstract

Concomitant with an increased number of memory-type cells, the amount of naive T cells steadily declines with age. Although the regulatory mechanisms behind this conversion are not fully understood, the suggestion is that both alterations in thymic output and homeostatic signals mold the naive T cell pool. In this study, we identify a new subset of circulating CD27highCD45RAhigh CD8+ T cells characterized by low IL-7Rα message and protein expression. Analysis of TCR repertoire and TCR excision circle content together with ex vivo recovery of IL-7Rα expression indicated that these cells should be placed into the naive T cell pool. Compared with conventional IL-7Rαhigh naive T cells, this subset displayed significantly lower levels of CD28 and higher levels of HLA-DR. Proliferative responses to anti-CD3/CD28 mAbs were indistinguishable from conventional naive T cells, but the responsiveness to IL-7 was limited. Strikingly, IL-7Rαlow naive T cells were particularly increased in circumstances of naive CD8+ T cells shortage, as in the elderly, in patients early after hemopoietic stem cell transplantation, and in HIV-infected individuals. As common γ chain cytokines induce rapid down-regulation of IL-7Rα, we propose that this new subset of naive T cells may encompass cells that have recently received homeostatic signals.