Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets
| Autor: | Robert Korngold, Claude Sportes, Michel Morre, Thomas A. Fleisher, Hua Zhang, Sarfraz Memon, Crystal L. Mackall, Terry J. Fry, Rebecca Babb, Catherine Chow, Renaud Buffet, Kevin S. Chua, Julie Engels, Robert J. Amato, Ronald E. Gress, David Venzon, Andrew L. Pecora, Margaret R. Brown, Frances T. Hakim, Michael Krumlauf |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Naive T cell T cell Immunology Receptors Antigen T-Cell HIV Infections CD8-Positive T-Lymphocytes Biology T-Lymphocytes Regulatory Article Lymphocyte Depletion Mice Interleukin 21 Neoplasms medicine Animals Humans Immunology and Allergy Cytotoxic T cell IL-2 receptor Interleukin-7 Age Factors HIV CD28 Articles Natural killer T cell Recombinant Proteins CD4 Lymphocyte Count Up-Regulation medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Female CD8 |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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