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Blood, 15 May 2001, Vol. 97, No. 10, pp. 2983-2990
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
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, and
Crystal L. Mackall
From the Pediatric Oncology Branch, Biostatistics and
Data Management Section, and HIV and AIDS Malignancy Branch of the
National Cancer Institute; and National Institute of Allergy and
Infectious Diseases; all of the National Institutes of Health,
Bethesda, MD; University of Colorado Health Sciences Center, Denver CO;
Case Western Reserve University School of Medicine and University
Hospitals of Cleveland, Cleveland, OH; Center for Biostatistics in AIDS
Research, Harvard School of Public Health, Boston, MA; and Rush Medical
College, Chicago IL.
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.
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