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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2855-2862. Prepublished online as a Blood First Edition Paper on December 15, 2005; DOI 10.1182/blood-2005-09-3560. This Article Full Text (PDF) All Versions of this Article: 2005-09-3560v1 107/7/2855    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kim, H.-R. Articles by Kang, I. Search for Related Content PubMed PubMed Citation Articles by Kim, H.-R. Articles by Kang, I. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 6, 2005 Accepted November 24, 2005 Altered IL-7R expression with aging and the potential implications of IL-7 therapy on CD8+ T cell immune responses Hang-Rae Kim, Myung Sun Hong, Jin Myung Dan, and Insoo Kang* Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA * Corresponding author; email: insoo.kang{at}yale.edu. We investigated the effect of aging on the IL-7-mediated CD8+ T cell survival pathway and IL-7 therapy on T cell immunity. Cells expressing IL-7 receptor (R)high and low were identified in CD45RA+ effector memory (EMCD45RA+, CD45RA+CCR7+) CD8+ T cell subsets. The elderly (age 65) had an increased frequency of EMCD45RA+ IL-7Rlow CD8+ T cells leading to decreased STAT5 phosphorylation and survival responses to IL-7 compared to the young (age 40). These EMCD45RA+ IL-7Rlow cells were largely antigen-experienced (CD27-CD28-), replicatively senescent (CD57+) and perforinhigh CD8+ T cells that had decreased IL-7R mRNA independent of guanine and adenine binding protein (GABP) and growth factor independence-1(GFI1) expression. In measuring T cell receptor (TCR) repertoires of EMCD45RA+ CD8+ T cells, the elderly had a limited repertoire in IL-7Rhigh and low cells, whereas the young had a diverse repertoire in IL-7Rhigh but not in IL-7Rlow cells. These findings suggest that aging affects IL-7R expression by EMCD45RA+ CD8+ T cells leading to impaired signaling and survival responses to IL-7 and that IL-7 therapy may improve the survival of EMCD45RA+ CD8+ T cells with a diverse TCR repertoire in the young but not in the elderly. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: IL-7 comes of age Terry J. Fry Blood 2006 107: 2587-2588. [Full Text] [PDF] This article has been cited by other articles: I. Ray-Coquard, C. Cropet, M. Van Glabbeke, C. Sebban, A. Le Cesne, I. Judson, O. Tredan, J. Verweij, P. Biron, I. Labidi, et al. Lymphopenia as a Prognostic Factor for Overall Survival in Advanced Carcinomas, Sarcomas, and Lymphomas Cancer Res., July 1, 2009; 69(13): 5383 - 5391. [Abstract] [Full Text] [PDF] C. Sportes, F. T. Hakim, S. A. Memon, H. Zhang, K. S. Chua, M. R. Brown, T. A. Fleisher, M. C. Krumlauf, R. R. Babb, C. K. Chow, et al. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets J. Exp. Med., July 7, 2008; 205(7): 1701 - 1714. [Abstract] [Full Text] [PDF] K. Ladell, M. K. Hellerstein, D. Cesar, R. Busch, D. Boban, and J. M. McCune Central Memory CD8+ T Cells Appear to Have a Shorter Lifespan and Reduced Abundance as a Function of HIV Disease Progression J. Immunol., June 15, 2008; 180(12): 7907 - 7918. [Abstract] [Full Text] [PDF] H. W. Lim and C. H. Kim Loss of IL-7 Receptor {alpha} on CD4+ T Cells Defines Terminally Differentiated B Cell-Helping Effector T Cells in a B Cell-Rich Lymphoid Tissue J. Immunol., December 1, 2007; 179(11): 7448 - 7456. [Abstract] [Full Text] [PDF] A. Vranjkovic, A. M. Crawley, K. Gee, A. Kumar, and J. B. Angel IL-7 decreases IL-7 receptor {alpha} (CD127) expression and induces the shedding of CD127 by human CD8+ T cells Int. Immunol., December 1, 2007; 19(12): 1329 - 1339. [Abstract] [Full Text] [PDF] H.-R. Kim, K.-A Hwang, and I. Kang Dual Roles of IL-15 in Maintaining IL-7R{alpha}lowCCR7 Memory CD8+ T Cells in Humans via Recovering the Phosphatidylinositol 3-Kinase/AKT Pathway J. Immunol., November 15, 2007; 179(10): 6734 - 6740. [Abstract] [Full Text] [PDF] S.-J. Lee, R. J. Rossi, S.-K. Lee, M. Croft, B. S. Kwon, R. S. Mittler, and A. T. Vella CD134 Costimulation Couples the CD137 Pathway to Induce Production of Supereffector CD8 T Cells That Become IL-7 Dependent J. Immunol., August 15, 2007; 179(4): 2203 - 2214. [Abstract] [Full Text] [PDF] H.-R. Kim, K.-A Hwang, K.-C. Kim, and I. Kang Down-Regulation of IL-7R{alpha} Expression in Human T Cells via DNA Methylation J. Immunol., May 1, 2007; 178(9): 5473 - 5479. [Abstract] [Full Text] [PDF] A. S. Albuquerque, C. S. Cortesao, R. B. Foxall, R. S. Soares, R. M. M. Victorino, and A. E. Sousa Rate of Increase in Circulating IL-7 and Loss of IL-7R{alpha} Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes J. Immunol., March 1, 2007; 178(5): 3252 - 3259. [Abstract] [Full Text] [PDF] T. W. LeBien Battling bone marrow B-lineage cells Blood, August 15, 2006; 108(4): 1120 - 1120. [Full Text] [PDF] L. Swainson, E. Verhoeyen, F.-L. Cosset, and N. Taylor IL-7R{alpha} Gene Expression Is Inversely Correlated with Cell Cycle Progression in IL-7-Stimulated T Lymphocytes. J. Immunol., June 1, 2006; 176(11): 6702 - 6708. [Abstract] [Full Text] [PDF]

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