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

Terry J. Fry, Elizabeth Connick, Judith Falloon, Michael M. Lederman, David J. Liewehr, John Spritzler, Seth M. Steinberg, Lauren V. Wood, Robert Yarchoan, Judy Zuckerman, Alan Landay, Crystal L. Mackall

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2983-2990
Number of pages8
JournalBlood
Volume97
Issue number10
DOIs
StatePublished - May 15 2001

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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