Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets
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- Claude Sportès
- 1Experimental Transplantation and Immunology Branch;
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- Frances T. Hakim
- 1Experimental Transplantation and Immunology Branch;
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- Sarfraz A. Memon
- 1Experimental Transplantation and Immunology Branch;
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- Hua Zhang
- 2Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute;
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- Kevin S. Chua
- 2Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute;
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- Margaret R. Brown
- 4Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892
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- Thomas A. Fleisher
- 4Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892
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- Michael C. Krumlauf
- 1Experimental Transplantation and Immunology Branch;
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- Rebecca R. Babb
- 1Experimental Transplantation and Immunology Branch;
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- Catherine K. Chow
- 3Departments of Radiology;
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- Terry J. Fry
- 2Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute;
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- Julie Engels
- 5Cytheris Inc., Rockville, MD 20850
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- Renaud Buffet
- 5Cytheris Inc., Rockville, MD 20850
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- Michel Morre
- 5Cytheris Inc., Rockville, MD 20850
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- Robert J. Amato
- 6Methodist Hospital, Texas Medical Center, Houston, TX 77021
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- David J. Venzon
- 7Biostatistics and Data Management Section, National Cancer Institute,
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- Robert Korngold
- 8The Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601
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- Andrew Pecora
- 8The Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601
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- Ronald E. Gress
- 1Experimental Transplantation and Immunology Branch;
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- Crystal L. Mackall
- 2Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute;
Abstract
<jats:p>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.</jats:p>
Journal
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 205 (7), 1701-1714, 2008-06-23
Rockefeller University Press
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Details 詳細情報について
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- CRID
- 1361418520246364160
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- ISSN
- 15409538
- 00221007
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- Data Source
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- Crossref