title: A potential role for interleukin-7 in T-cell homeostasis.
abstract: Interleukin (IL)-7 is known to up-regulate thymopoietic pathways of T-cell regeneration. Recent work also has shown it to potently enhance thymic-independent peripheral expansion and to restore immunocompetence 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 pediatric (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 homeostasis following T-cell depletion.
authors.affiliation: Pediatric Oncology Branch, Biostatistics and Data Management Section, and HIV and AIDS Malignancy Branch of the National Cancer Institute, the National Institutes of Health, Bethesda, MD, USA. tf60y@nih.gov
authors.forename: T J
authors.initials: TJ
authors.lastname: Fry
authors.forename: E
authors.initials: E
authors.lastname: Connick
authors.forename: J
authors.initials: J
authors.lastname: Falloon
authors.forename: M M
authors.initials: MM
authors.lastname: Lederman
authors.forename: D J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: J
authors.initials: J
authors.lastname: Spritzler
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: L V
authors.initials: LV
authors.lastname: Wood
authors.forename: R
authors.initials: R
authors.lastname: Yarchoan
authors.forename: J
authors.initials: J
authors.lastname: Zuckerman
authors.forename: A
authors.initials: A
authors.lastname: Landay
authors.forename: C L
authors.initials: CL
authors.lastname: Mackall
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D007223:Infant; D015851:Interleukin-7 / Q000097:blood / Q000502:physiology*; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D019438:Ritonavir / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D017320:HIV Protease Inhibitors; D015851:Interleukin-7; D019438:Ritonavir