Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Judge, A. D. Articles by Sprent, J. Search for Related Content PubMed PubMed Citation Articles by Judge, A. D. Articles by Sprent, J. Social Bookmarking                      What's this?

Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

Address correspondence to Jonathan Sprent, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: 858-784-8619; Fax: 858-784-8839; E-mail: jsprent{at}scripps.edu

Previous work has shown that memory-phenotype CD44^hi CD8⁺ cells are controlled by a cytokine, interleukin (IL)-15. However, the dependency of CD44^hi CD8⁺ cells on IL-15 is partial rather than complete. Here, evidence is presented that CD44^hi CD8⁺ cells comprise a mixed population of IL-15–dependent and IL-15–independent cells. The major subset of CD122^hi CD44^hi CD8⁺ cells is heavily dependent on IL-15 by three different parameters, namely (1) "bystander" proliferation induced via IFN-induced stimulation of the innate immune system, (2) normal "background" proliferation, and (3) T cell survival; IL-15 dependency is most extreme for the Ly49⁺ subset of CD122^hi CD44^hi CD8⁺ cells. In contrast to CD122^hi cells, the CD122^lo subset of CD44^hi CD8⁺ cells is IL-15 independent; likewise, being CD122^lo, CD44^hi CD4⁺ cells are IL-15 independent. Thus, subsets of memory-phenotype T cells differ radically in their sensitivity to IL-15.

Key Words: IL-15 • T cell subsets • CD122 • CD44 • memory

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Motegi, A., Kinoshita, M., Inatsu, A., Habu, Y., Saitoh, D., Seki, S. (2008). IL-15-induced CD8+CD122+ T cells increase antibacterial and anti-tumor immune responses: implications for immune function in aged mice. J. Leukoc. Biol. 84: 1047-1056 [Abstract] [Full Text]  
• Elyaman, W., Kivisakk, P., Reddy, J., Chitnis, T., Raddassi, K., Imitola, J., Bradshaw, E., Kuchroo, V. K., Yagita, H., Sayegh, M. H., Khoury, S. J. (2008). Distinct Functions of Autoreactive Memory and Effector CD4+ T Cells in Experimental Autoimmune Encephalomyelitis. Am. J. Pathol. 173: 411-422 [Abstract] [Full Text]  
• Miyagawa, F., Tagaya, Y., Kim, B. S., Patel, H. J., Ishida, K., Ohteki, T., Waldmann, T. A., Katz, S. I. (2008). IL-15 Serves as a Costimulator in Determining the Activity of Autoreactive CD8 T Cells in an Experimental Mouse Model of Graft-versus-Host-Like Disease. J. Immunol. 181: 1109-1119 [Abstract] [Full Text]  
• Rapetti, L., Meunier, S., Pontoux, C., Tanchot, C. (2008). CD4 Help Regulates Expression of Crucial Genes Involved in CD8 T Cell Memory and Sensitivity to Regulatory Elements. J. Immunol. 181: 299-308 [Abstract] [Full Text]  
• Halwani, R., Boyer, J. D., Yassine-Diab, B., Haddad, E. K., Robinson, T. M., Kumar, S., Parkinson, R., Wu, L., Sidhu, M. K., Phillipson-Weiner, R., Pavlakis, G. N., Felber, B. K., Lewis, M. G., Shen, A., Siliciano, R. F., Weiner, D. B., Sekaly, R.-P. (2008). Therapeutic Vaccination with Simian Immunodeficiency Virus (SIV)-DNA+IL-12 or IL-15 Induces Distinct CD8 Memory Subsets in SIV-Infected Macaques. J. Immunol. 180: 7969-7979 [Abstract] [Full Text]  
• Oh, S., Perera, L. P., Terabe, M., Ni, L., Waldmann, T. A., Berzofsky, J. A. (2008). IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis. Proc. Natl. Acad. Sci. USA 105: 5201-5206 [Abstract] [Full Text]  
• Dubois, S., Patel, H. J., Zhang, M., Waldmann, T. A., Muller, J. R. (2008). Preassociation of IL-15 with IL-15R{alpha}-IgG1-Fc Enhances Its Activity on Proliferation of NK and CD8+/CD44high T Cells and Its Antitumor Action. J. Immunol. 180: 2099-2106 [Abstract] [Full Text]  
• Yang, T., Wall, E. M., Milne, K., Theiss, P., Watson, P., Nelson, B. H. (2007). CD8+ T Cells Induce Complete Regression of Advanced Ovarian Cancers by an Interleukin (IL)-2/IL-15 Dependent Mechanism. Clin. Cancer Res. 13: 7172-7180 [Abstract] [Full Text]  
• Kim, H.-R., Hwang, K.-A, Kang, I. (2007). 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. 179: 6734-6740 [Abstract] [Full Text]  
• Liu, S., Lizee, G., Lou, Y., Liu, C., Overwijk, W. W., Wang, G., Hwu, P. (2007). IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells. Int Immunol 19: 1213-1221 [Abstract] [Full Text]  
• Cho, J.-H., Boyman, O., Kim, H.-O., Hahm, B., Rubinstein, M. P., Ramsey, C., Kim, D. M., Surh, C. D., Sprent, J. (2007). An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2. J. Exp. Med. 204: 1787-1801 [Abstract] [Full Text]  
• Jenkins, M. R., Kedzierska, K., Doherty, P. C., Turner, S. J. (2007). Heterogeneity of Effector Phenotype for Acute Phase and Memory Influenza A Virus-Specific CTL. J. Immunol. 179: 64-70 [Abstract] [Full Text]  
• Sandau, M. M., Winstead, C. J., Jameson, S. C. (2007). IL-15 Is Required for Sustained Lymphopenia-Driven Proliferation and Accumulation of CD8 T Cells. J. Immunol. 179: 120-125 [Abstract] [Full Text]  
• Purton, J. F., Tan, J. T., Rubinstein, M. P., Kim, D. M., Sprent, J., Surh, C. D. (2007). Antiviral CD4+ memory T cells are IL-15 dependent. J. Exp. Med. 204: 951-961 [Abstract] [Full Text]  
• Tanaka, K., Sawamura, S., Satoh, T., Kobayashi, K., Noda, S. (2007). Role of the Indigenous Microbiota in Maintaining the Virus-Specific CD8 Memory T Cells in the Lung of Mice Infected with Murine Cytomegalovirus. J. Immunol. 178: 5209-5216 [Abstract] [Full Text]  
• Osborne, L. C., Dhanji, S., Snow, J. W., Priatel, J. J., Ma, M. C., Miners, M. J., Teh, H.-S., Goldsmith, M. A., Abraham, N. (2007). Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7R{alpha} mutant mice. J. Exp. Med. 204: 619-631 [Abstract] [Full Text]  
• McDyer, J. F. (2007). Human and Murine Obliterative Bronchiolitis in Transplant. Proc Am Thorac Soc 4: 37-43 [Abstract] [Full Text]  
• Sheridan, B. S., Khanna, K. M., Frank, G. M., Hendricks, R. L. (2006). Latent Virus Influences the Generation and Maintenance of CD8+ T Cell Memory. J. Immunol. 177: 8356-8364 [Abstract] [Full Text]  
• Ohteki, T., Tada, H., Ishida, K., Sato, T., Maki, C., Yamada, T., Hamuro, J., Koyasu, S. (2006). Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo. J. Exp. Med. 203: 2329-2338 [Abstract] [Full Text]  
• Obar, J. J., Fuse, S., Leung, E. K., Bellfy, S. C., Usherwood, E. J. (2006). Gammaherpesvirus persistence alters key CD8 T-cell memory characteristics and enhances antiviral protection.. J. Virol. 80: 8303-8315 [Abstract] [Full Text]  
• Boyman, O., Cho, J.-H., Tan, J. T., Surh, C. D., Sprent, J. (2006). A major histocompatibility complex class I-dependent subset of memory phenotype CD8+ cells. J. Exp. Med. 203: 1817-1825 [Abstract] [Full Text]  
• Bolesta, E., Kowalczyk, A., Wierzbicki, A., Eppolito, C., Kaneko, Y., Takiguchi, M., Stamatatos, L., Shrikant, P. A., Kozbor, D. (2006). Increased Level and Longevity of Protective Immune Responses Induced by DNA Vaccine Expressing the HIV-1 Env Glycoprotein when Combined with IL-21 and IL-15 Gene Delivery. J. Immunol. 177: 177-191 [Abstract] [Full Text]  
• Rubinstein, M. P., Kovar, M., Purton, J. F., Cho, J.-H., Boyman, O., Surh, C. D., Sprent, J. (2006). Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha}. Proc. Natl. Acad. Sci. USA 103: 9166-9171 [Abstract] [Full Text]  
• Shi, M., Xiang, J. (2006). CD4+ T cell-independent maintenance and expansion of memory CD8+ T cells derived from in vitro dendritic cell activation. Int Immunol 18: 887-895 [Abstract] [Full Text]  
• Bianchi, T., Gasser, S., Trumpp, A., MacDonald, H. R. (2006). c-Myc acts downstream of IL-15 in the regulation of memory CD8 T-cell homeostasis. Blood 107: 3992-3999 [Abstract] [Full Text]  
• Su, H., Chang, D. S., Gambhir, S. S., Braun, J. (2006). Monitoring the Antitumor Response of Naive and Memory CD8 T Cells in RAG1-/- Mice by Positron-Emission Tomography. J. Immunol. 176: 4459-4467 [Abstract] [Full Text]  
• Kim, H.-R., Hong, M. S., Dan, J. M., Kang, I. (2006). Altered IL-7R{alpha} expression with aging and the potential implications of IL-7 therapy on CD8+ T-cell immune responses. Blood 107: 2855-2862 [Abstract] [Full Text]  
• Sun, A., Wei, H., Sun, R., Xiao, W., Yang, Y., Tian, Z. (2006). Human Interleukin-15 Improves Engraftment of Human T Cells in NOD-SCID Mice. CVI 13: 227-234 [Abstract] [Full Text]  
• Ely, K. H., Cookenham, T., Roberts, A. D., Woodland, D. L. (2006). Memory T Cell Populations in the Lung Airways Are Maintained by Continual Recruitment. J. Immunol. 176: 537-543 [Abstract] [Full Text]  
• Wang, L.-X., Li, R., Yang, G., Lim, M., O'Hara, A., Chu, Y., Fox, B. A., Restifo, N. P., Urba, W. J., Hu, H.-M. (2005). Interleukin-7-Dependent Expansion and Persistence of Melanoma-Specific T Cells in Lymphodepleted Mice Lead to Tumor Regression and Editing. Cancer Res. 65: 10569-10577 [Abstract] [Full Text]  
• Gattinoni, L., Finkelstein, S. E., Klebanoff, C. A., Antony, P. A., Palmer, D. C., Spiess, P. J., Hwang, L. N., Yu, Z., Wrzesinski, C., Heimann, D. M., Surh, C. D., Rosenberg, S. A., Restifo, N. P. (2005). Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J. Exp. Med. 202: 907-912 [Abstract] [Full Text]  
• Nishimura, H., Yajima, T., Muta, H., Podack, E. R., Tani, K., Yoshikai, Y. (2005). A Novel Role of CD30/CD30 Ligand Signaling in the Generation of Long-Lived Memory CD8+ T Cells. J. Immunol. 175: 4627-4634 [Abstract] [Full Text]  
• Woodland, D. L., Scott, I. (2005). T Cell Memory in the Lung Airways. Proc Am Thorac Soc 2: 126-131 [Abstract] [Full Text]  
• Kutzler, M. A., Robinson, T. M., Chattergoon, M. A., Choo, D. K., Choo, A. Y., Choe, P. Y., Ramanathan, M. P., Parkinson, R., Kudchodkar, S., Tamura, Y., Sidhu, M., Roopchand, V., Kim, J. J., Pavlakis, G. N., Felber, B. K., Waldmann, T. A., Boyer, J. D., Weiner, D. B. (2005). Coimmunization with an Optimized IL-15 Plasmid Results in Enhanced Function and Longevity of CD8 T Cells That Are Partially Independent of CD4 T Cell Help. J. Immunol. 175: 112-123 [Abstract] [Full Text]  
• Li, Y., Zhi, W., Wareski, P., Weng, N.-p. (2005). IL-15 Activates Telomerase and Minimizes Telomere Loss and May Preserve the Replicative Life Span of Memory CD8+ T Cells In Vitro. J. Immunol. 174: 4019-4024 [Abstract] [Full Text]  
• Kamath, A. T., Sheasby, C. E., Tough, D. F. (2005). Dendritic Cells and NK Cells Stimulate Bystander T Cell Activation in Response to TLR Agonists through Secretion of IFN-{alpha}{beta} and IFN-{gamma}. J. Immunol. 174: 767-776 [Abstract] [Full Text]  
• Kobayashi, H., Dubois, S., Sato, N., Sabzevari, H., Sakai, Y., Waldmann, T. A., Tagaya, Y. (2005). Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 105: 721-727 [Abstract] [Full Text]  
• Alpdogan, O., Eng, J. M., Muriglan, S. J., Willis, L. M., Hubbard, V. M., Tjoe, K. H., Terwey, T. H., Kochman, A., van den Brink, M. R. M. (2005). Interleukin-15 enhances immune reconstitution after allogeneic bone marrow transplantation. Blood 105: 865-873 [Abstract] [Full Text]  
• Blaser, B. W., Roychowdhury, S., Kim, D. J., Schwind, N. R., Bhatt, D., Yuan, W., Kusewitt, D. F., Ferketich, A. K., Caligiuri, M. A., Guimond, M. (2005). Donor-derived IL-15 is critical for acute allogeneic graft-versus-host disease. Blood 105: 894-901 [Abstract] [Full Text]  
• Zeng, R., Spolski, R., Finkelstein, S. E., Oh, S., Kovanen, P. E., Hinrichs, C. S., Pise-Masison, C. A., Radonovich, M. F., Brady, J. N., Restifo, N. P., Berzofsky, J. A., Leonard, W. J. (2005). Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J. Exp. Med. 201: 139-148 [Abstract] [Full Text]  
• Wysocka, M., Benoit, B. M., Newton, S., Azzoni, L., Montaner, L. J., Rook, A. H. (2004). Enhancement of the host immune responses in cutaneous T-cell lymphoma by CpG oligodeoxynucleotides and IL-15. Blood 104: 4142-4149 [Abstract] [Full Text]  
• Kamimura, D., Ueda, N., Sawa, Y., Hachida, S., Atsumi, T., Nakagawa, T., Sawa, S.-i., Jin, G.-H., Suzuki, H., Ishihara, K., Murakami, M., Hirano, T. (2004). Evidence of a Novel IL-2/15R{beta}-Targeted Cytokine Involved in Homeostatic Proliferation of Memory CD8+ T Cells. J. Immunol. 173: 6041-6049 [Abstract] [Full Text]  
• Corbin, G. A., Harty, J. T. (2004). Duration of Infection and Antigen Display Have Minimal Influence on the Kinetics of the CD4+ T Cell Response to Listeria monocytogenes Infection. J. Immunol. 173: 5679-5687 [Abstract] [Full Text]  
• Burkett, P. R., Koka, R., Chien, M., Chai, S., Boone, D. L., Ma, A. (2004). Coordinate Expression and Trans Presentation of Interleukin (IL)-15R{alpha} and IL-15 Supports Natural Killer Cell and Memory CD8+ T Cell Homeostasis. J. Exp. Med. 200: 825-834 [Abstract] [Full Text]  
• Anfossi, N., Robbins, S. H., Ugolini, S., Georgel, P., Hoebe, K., Bouneaud, C., Ronet, C., Kaser, A., DiCioccio, C. B., Tomasello, E., Blumberg, R. S., Beutler, B., Reiner, S. L., Alexopoulou, L., Lantz, O., Raulet, D. H., Brossay, L., Vivier, E. (2004). Expansion and Function of CD8+ T Cells Expressing Ly49 Inhibitory Receptors Specific for MHC Class I Molecules. J. Immunol. 173: 3773-3782 [Abstract] [Full Text]  
• Obar, J. J., Crist, S. G., Leung, E. K., Usherwood, E. J. (2004). IL-15-Independent Proliferative Renewal of Memory CD8+ T Cells in Latent Gammaherpesvirus Infection. J. Immunol. 173: 2705-2714 [Abstract] [Full Text]  
• Lenz, D. C., Kurz, S. K., Lemmens, E., Schoenberger, S. P., Sprent, J., Oldstone, M. B. A., Homann, D. (2004). IL-7 regulates basal homeostatic proliferation of antiviral CD4+T cell memory. Proc. Natl. Acad. Sci. USA 101: 9357-9362 [Abstract] [Full Text]  
• Carrio, R., Bathe, O. F., Malek, T. R. (2004). Initial Antigen Encounter Programs CD8+ T Cells Competent to Develop into Memory Cells That Are Activated in an Antigen-Free, IL-7- and IL-15-Rich Environment. J. Immunol. 172: 7315-7323 [Abstract] [Full Text]  
• Nakagawa, R., Inui, T., Nagafune, I., Tazunoki, Y., Motoki, K., Yamauchi, A., Hirashima, M., Habu, Y., Nakashima, H., Seki, S. (2004). Essential Role of Bystander Cytotoxic CD122+CD8+ T Cells for the Antitumor Immunity Induced in the Liver of Mice by {alpha}-Galactosylceramide. J. Immunol. 172: 6550-6557 [Abstract] [Full Text]  
• Koschella, M., Voehringer, D., Pircher, H. (2004). CD40 Ligation In Vivo Induces Bystander Proliferation of Memory Phenotype CD8 T Cells. J. Immunol. 172: 4804-4811 [Abstract] [Full Text]  
• Huster, K. M., Busch, V., Schiemann, M., Linkemann, K., Kerksiek, K. M., Wagner, H., Busch, D. H. (2004). Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8+ memory T cell subsets. Proc. Natl. Acad. Sci. USA 101: 5610-5615 [Abstract] [Full Text]  
• Schluns, K. S., Nowak, E. C., Cabrera-Hernandez, A., Puddington, L., Lefrancois, L., Aguila, H. L. (2004). Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor {alpha} expression. Proc. Natl. Acad. Sci. USA 101: 5616-5621 [Abstract] [Full Text]  
• Neely, G. G., Epelman, S., Ma, L. L., Colarusso, P., Howlett, C. J., Amankwah, E. K., McIntyre, A. C., Robbins, S. M., Mody, C. H. (2004). Monocyte Surface-Bound IL-15 Can Function as an Activating Receptor and Participate in Reverse Signaling. J. Immunol. 172: 4225-4234 [Abstract] [Full Text]  
• Khanolkar, A., Fuller, M. J., Zajac, A. J. (2004). CD4 T Cell-Dependent CD8 T Cell Maturation. J. Immunol. 172: 2834-2844 [Abstract] [Full Text]  
• Klebanoff, C. A., Finkelstein, S. E., Surman, D. R., Lichtman, M. K., Gattinoni, L., Theoret, M. R., Grewal, N., Spiess, P. J., Antony, P. A., Palmer, D. C., Tagaya, Y., Rosenberg, S. A., Waldmann, T. A., Restifo, N. P. (2004). IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T Cells. Proc. Natl. Acad. Sci. USA 101: 1969-1974 [Abstract] [Full Text]  
• Obar, J. J., Crist, S. G., Gondek, D. C., Usherwood, E. J. (2004). Different Functional Capacities of Latent and Lytic Antigen-Specific CD8 T Cells in Murine Gammaherpesvirus Infection. J. Immunol. 172: 1213-1219 [Abstract] [Full Text]  
• Kondrack, R. M., Harbertson, J., Tan, J. T., McBreen, M. E., Surh, C. D., Bradley, L. M. (2003). Interleukin 7 Regulates the Survival and Generation of Memory CD4 Cells. J. Exp. Med. 198: 1797-1806 [Abstract] [Full Text]  
• Ortiz-Suarez, A., Miller, R. A. (2003). Antigen-Independent Expansion of CD28hi CD8 Cells From Aged Mice: Cytokine Requirements and Signal Transduction Pathways. J. Gerontol. A Biol. Sci. Med. Sci. 58: B1063-1073 [Abstract] [Full Text]  
• Ely, K. H., Roberts, A. D., Woodland, D. L. (2003). Cutting Edge: Effector Memory CD8+ T Cells in the Lung Airways Retain the Potential to Mediate Recall Responses. J. Immunol. 171: 3338-3342 [Abstract] [Full Text]  
• Jiang, J., Anaraki, F., Blank, K. J., Murasko, D. M. (2003). Cutting Edge: T Cells from Aged Mice Are Resistant to Depletion Early During Virus Infection. J. Immunol. 171: 3353-3357 [Abstract] [Full Text]  
• Lakkis, F. G., Sayegh, M. H. (2003). Memory T Cells: A Hurdle to Immunologic Tolerance. J. Am. Soc. Nephrol. 14: 2402-2410 [Full Text]  
• Tritel, M., Stoddard, A. M., Flynn, B. J., Darrah, P. A., Wu, C.-y., Wille, U., Shah, J. A., Huang, Y., Xu, L., Betts, M. R., Nabel, G. J., Seder, R. A. (2003). Prime-Boost Vaccination with HIV-1 Gag Protein and Cytosine Phosphate Guanosine Oligodeoxynucleotide, Followed by Adenovirus, Induces Sustained and Robust Humoral and Cellular Immune Responses. J. Immunol. 171: 2538-2547 [Abstract] [Full Text]  
• Berenzon, D., Schwenk, R. J., Letellier, L., Guebre-Xabier, M., Williams, J., Krzych, U. (2003). Protracted Protection to Plasmodium berghei Malaria Is Linked to Functionally and Phenotypically Heterogeneous Liver Memory CD8+ T Cells. J. Immunol. 171: 2024-2034 [Abstract] [Full Text]  
• Geginat, J., Lanzavecchia, A., Sallusto, F. (2003). Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines. Blood 101: 4260-4266 [Abstract] [Full Text]  
• Berard, M., Brandt, K., Paus, S. B., Tough, D. F. (2003). IL-15 Promotes the Survival of Naive and Memory Phenotype CD8+ T Cells. J. Immunol. 170: 5018-5026 [Abstract] [Full Text]  
• Burkett, P. R., Koka, R., Chien, M., Chai, S., Chan, F., Ma, A., Boone, D. L. (2003). IL-15Ralpha expression on CD8+ T cells is dispensable for T cell memory. Proc. Natl. Acad. Sci. USA 100: 4724-4729 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS