The Many Faces of IL-7: From Lymphopoiesis to Peripheral T Cell Maintenance

Abstract

IL-7 is well known as a lymphopoietic cytokine, but recent studies have also identified a critical role for IL-7 in peripheral T cell homeostasis. IL-7 is well poised to serve as a homeostatic cytokine because it is produced by resting stromal cells, the IL-7R is present on most T cells, and IL-7 down-regulates its own receptor. These features allow IL-7 to signal large numbers of resting T cells and to be efficiently used when supplies are limiting. Consistent with this, in normal hosts, IL-7 is required for survival of naive T cell populations, and IL-7 contributes to homeostatic cycling of naive and memory cells. In addition, lymphopenic hosts accumulate increased levels of IL-7, and the supranormal levels are largely responsible for inducing homeostatic peripheral expansion in response to lymphopenia. Thus, IL-7 plays critical and nonredundant roles in both T cell lymphopoiesis and in maintaining and restoring peripheral T cell homeostasis.

Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

“…However, activated OT-II T cells respond in vitro only to IL-2 and IL-7, with no effect of IFN-g, arguing against direct involvement of inflammatory cytokines in bystander proliferation. IL-7, unlike other members of the g c cytokine family induced during immune responses, is constitutively produced at low levels in non-lymphoid and lymphoid organs by not yet well-characterized stromal cells [23][24][25]. Interestingly, activated OT-II cells expressed IL-7Ra and this cytokine was effective in inducing proliferation of activated OT-II cells in vitro.…”

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

“…Giving IL‐15 may have additional benefits of increasing NK cell and dendritic cell survival, whereas IL‐7 is thought to be a cytokine that is targeted more toward T cells. IL‐7 is a multifunctional cytokine of the immune system that affects both T cells and B cells and induces the proliferation of naïve and memory T cells 44. Venet et al45 showed that IL‐7 treatment of isolated lymphocytes from septic patients restored T‐cell proliferation and IFN‐γ secretion.…”

Acute Thymic Involution and Mechanisms for Recovery

“…Notably, application of IL-7 has been reported to enhance immune reconstitution during lymphopenia. IL-7 therapy is thus a significant factor for enhancing the actual thymic throughput (Fry and Mackall 2005). Recombinant IL-7 therapy enhances the total numbers of T stem cells and restores the diversity of the T cell repertoire following cytotoxic chemotherapy in human beings (Zhang et al 2015).…”