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¹ Experimental Transplantation and Immunology Branch; ² Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute; ³ Departments of Radiology; ⁴ Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892
⁵ Cytheris Inc., Rockville, MD 20850
⁶ Methodist Hospital, Texas Medical Center, Houston, TX 77021
⁷ Biostatistics and Data Management Section, National Cancer Institute, ⁸ The Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601

CORRESPONDENCE Claude Sportès: csportes{at}mail.nih.gov

Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during T cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on T cell immune reconstitution in mice and primates. First-in-human clinical studies of recombinant human IL-7 (rhIL-7) provided the opportunity to investigate the effects of IL-7 therapy on lymphocytes in vivo. rhIL-7 induced in vivo T cell cycling, bcl-2 up-regulation, and a sustained increase in peripheral blood CD4⁺ and CD8⁺ T cells. This T cell expansion caused a significant broadening of circulating T cell receptor (TCR) repertoire diversity independent of the subjects' age as naive T cells, including recent thymic emigrants (RTEs), expanded preferentially, whereas the proportions of regulatory T (T reg) cells and senescent CD8⁺ effectors diminished. The resulting composition of the circulating T cell pool more closely resembled that seen earlier in life. This profile, distinctive among cytokines under clinical development, suggests that rhIL-7 therapy could enhance and broaden immune responses, particularly in individuals with limited naive T cells and diminished TCR repertoire diversity, as occurs after physiological (age), pathological (human immunodeficiency virus), or iatrogenic (chemotherapy) lymphocyte depletion.

Abbreviations used: CT, computerized tomography; c, common chain; rh, recombinant human; MFI, mean fluorescence intensity; RTE, recent thymic emigrant; TREC, TCR excision circle.

R.E. Gress and C.L. Mackall contributed equally to this paper.

© 2008 Sportès et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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