A potential role for interleukin-7 in T-cell homeostasis

Abstract

Interleukin (IL)-7 is known to up-regulate thymopoietic pathways of T-cell regenera-tion. Recent work also has shown it to potently enhance thymic-independent peripheral expansion and to restore immu-nocompetence in athymic T-cell-depleted hosts. We hypothesized that endogenous IL-7 could contribute to the restoration of T-cell homeostasis following T-cell depletion. To analyze this, we evaluated circulating IL-7 levels and lymphocyte subsets in multiple clinical cohorts with T-cell depletion of varying etiologies. In pediat-ric (n 41) and adult (n 51) human immunodeficiency virus-infected CD4-depleted patients, there were strong inverse correlations between IL-7 levels and CD4 counts (r 0.77, P < .0001, and r 0.68, P < .0001). Declines in IL-7 were temporally correlated with recovery of CD4 counts. Similar patterns were observed in CD4-depleted patients receiving cancer chemotherapy (r 0.65, P .009). Therefore, in 2 disparate clinical scenarios involving CD4 depletion, IL-7 levels dynamically respond to changes in CD4 T-cell number, making this cytokine uniquely suited as a candidate regulator of T-cell homeostasis. Furthermore , in patients with idiopathic CD4 lymphopenia, a much weaker relationship between IL-7 levels and peripheral blood CD4 counts was observed, suggesting that an impaired IL-7 response to CD4 depletion may contribute to the impaired lymphocyte homeostasis observed in this population. In light of the known effects of IL-7 on T-cell regeneration, we postulate that increased availability of IL-7 could play a critical role in restoring T-cell ho-meostasis following T-cell depletion. (Blood. 2001;97:2983-2990)

Differential Effects of Interleukin-7 and Interleukin-15 on NK Cell Anti-Human Immunodeficiency Virus Activity

“…In patients with HIV infection, IL-7 levels are inversely correlated with CD4 T-cell lymphopenia, raising the possibility that IL-7 is a naturally occurring homeostatic response (52), a suggestion which is supported by a similar inverse correlation between IL-7 levels and CD4 T-cell numbers in patients with idiopathic CD4 lymphopenia and chemotherapy-induced myeloablation (26). IL-7 augments T-cell num-bers by two distinct means: the expansion of existing T cells (2) and enhanced de novo T-cell synthesis, as indicated by increased T-cell receptor excision circle frequency (53).…”

Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice

“…There is growing interest in the clinical application of potential immunomodulators such as IL-7 to enhance T cell production and survival in the setting of human immunodeficiency (11,20,47,48). In this report, we have characterized the specific survival signals furnished by IL-7 to various thymocyte subpopulations and have examined the impact of IL-7 treatment on thymocyte survival and on viral replication in the HIV-infected human thymus.…”

Interleukin-15 but Not Interleukin-7 Abrogates Vaccine-Induced Decrease in Virus Level in Simian Immunodeficiency Virusmac251-Infected Macaques

“…In contrast, IL-7 availability is increased during primary HIV-1 infection and persists, likely as a response to or as a cause of lymphopenia. Indeed, IL-7 levels are inversely correlated with CD4 ϩ T cell counts (33)(34)(35)(36).…”