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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.

© 2001 by The American Society of Hematology.
 

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Blood, May 1, 2002; 99(9): 3310 - 3318.
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J. Virol.Home page
A. Llano, J. Barretina, A. Gutierrez, J. Blanco, C. Cabrera, B. Clotet, and J. A. Este
Interleukin-7 in Plasma Correlates with CD4 T-Cell Depletion and May Be Associated with Emergence of Syncytium-Inducing Variants in Human Immunodeficiency Virus Type 1-Positive Individuals
J. Virol., November 1, 2001; 75(21): 10319 - 10325.
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JEMHome page
A. R.M. Almeida, J. A.M. Borghans, and A. A. Freitas
T Cell Homeostasis: Thymus Regeneration and Peripheral T Cell Restoration in Mice with a Reduced Fraction of Competent Precursors
J. Exp. Med., August 27, 2001; 194(5): 591 - 600.
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