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1887

Journal of General Virology header logo Journal of General Virology

Volume 88, Issue 2

Influence of interleukin-15 on CD8 natural killer cells in human immunodeficiency virus type 1-infected chimpanzees No Access

Abstract

Chimpanzees are susceptible to human immunodeficiency virus type-1 (HIV-1) and develop persistent infection but generally do not progress to full-blown AIDS. Several host and immunological factors have been implicated in mediating resistance to disease progression. Chimpanzees have a higher prevalence of circulating natural killer (NK) cells than humans; however, their role in mediating resistance to disease progression is not well understood. Furthermore, NK cell survival and activity have been shown to be dependent on interleukin-15 (IL-15). Accordingly, the influence of IL-15 on NK cell activity and gamma interferon (IFN-) production was evaluated in naive and HIV-1-infected chimpanzees. stimulation of whole-blood cultures with recombinant gp120 (rgp120) resulted in enhanced IFN- production predominantly by the CD3 CD8 subset of NK cells, and addition of anti-IL-15 to the system decreased IFN- production. Moreover, stimulation with recombinant IL-15 (rIL-15) augmented IFN- production from this subset of NK cells and increased NK cell cytotoxic activity. Stimulation with rgp120 also resulted in a 2- to 7-fold increase in IL-15 production. These findings suggest that chimpanzee CD3 CD8 NK cells play a vital role in controlling HIV-1 infection by producing high levels of IFN-, and that IL-15 elicits IFN- production in this subpopulation of NK cells in HIV-1-infected chimpanzees.

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2007-02-01
2025-01-13
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References

  1. Addo M. M., Yu X. G., Rathod A., Cohen D., Eldridge R. L., Strick D., Johnston M. N., Corcoran C., Wurcel A. G. other authors 2003; Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J Virol 77:2081–2092 [CrossRef]
     [Google Scholar]
  2. Ahmad R., Sindhu S. T., Toma E., Morisset R., Ahamad A. 2003; Studies on the production of IL-15 in HIV infected/AIDS patients. J Clin Immunol 23:81–90 [CrossRef]
     [Google Scholar]
  3. Alter G., Malenfant J. M., Delabre R. M., Burgett N. C., Yu X. G., Lichterfeld M., Zaunders J., Altfeld M. 2004; Increased natural killer cell activity in viremic HIV-1 infection. J Immunol 173:5305–5311 [CrossRef]
     [Google Scholar]
  4. Azzoni L., Papasavvas E., Chehimi J., Kostman J. R., Mounzer K., Ondercin J., Perussia B., Montaner L. J. 2002; Sustained impairment of IFN- γ secretion in suppressed HIV-infected patients despite mature NK cell recovery: evidence for a defective reconstitution of innate immunity. J Immunol 168:5764–5770 [CrossRef]
     [Google Scholar]
  5. Balla-Jhagjhoorsingh S. S., Koopman G., Mooij P., Haaksama T. G. M., Teeuwsen V. J. P., Bontrop R. E., Heeney J. L. 1999; Conserved CTL epitopes shared between HIV-infected human long-term survivors and chimpanzees. J Immunol 162:2308–2314
     [Google Scholar]
  6. Bamford R. N., Battiata A. P., Burton J. D., Sharma H., Waldmann T. A. 1996; Interleukin (IL) 15/IL-T production by the adult T-cell lymphotrophic virus type I R region/IL-15 fusion message that lacks many upstream AUGs that normally attenuate IL-15 mRNA translation. Proc Natl Acad Sci U S A 93:2897–2902 [CrossRef]
     [Google Scholar]
  7. Betts M. R., Ambrozak D. R., Douek D. C., Bonhoeffer S., Brenchley J. M., Casazza J. P., Koup R. A., Picker L. J. 2001; Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses: relationship to viral load in untreated HIV infection. J Virol 75:11983–11991 [CrossRef]
     [Google Scholar]
  8. Castelli J., Thomas E. K., Gilliet M., Liu Y., Levy J. A. 2004; Mature dendritic cells can enhance CD8+ cell noncytotoxic anti-HIV responses: the role of IL-15. Blood 103:2699–2704 [CrossRef]
     [Google Scholar]
  9. Castro B. A., Homsy J., Lennette E., Murthy K. K., Eichberg J. W., Levy J. A. 1992; HIV-1 expression in chimpanzees can be activated by CD8+ cell depletion of CMV infection. Clin Immunol Immunopathol 65:227–233 [CrossRef]
     [Google Scholar]
  10. Davis I. C., Girard M., Fultz P. N. 1998; Loss of CD4+ T cells in human immunodeficiency virus type-1 infected chimpanzees is associated with increased lymphocyte apoptosis. J Virol 72:4623–4632
     [Google Scholar]
  11. Di Rienzo A. M., Furlini G., Olivier R., Ferris S., Heeney J., Montagnier L. 1994; Different proliferative response of human and chimpanzee lymphocyte after contact with human immunodeficiency virus type 1 gp120. Eur J Immunol 24:34–40 [CrossRef]
     [Google Scholar]
  12. Droge W., Murthy K. K., Stahl-Hennig C., Hartung S., Plesker R., Rouse S., Peterhans E., Kinscherf R., Fischbach T., Eck H. P. 1993; Plasma amino acid dysregulation after lentiviral infection. AIDS Res Hum Retroviruses 9:807–809 [CrossRef]
     [Google Scholar]
  13. Dunne J., Lynch S., O'Farrelly C., Todryk S., Hegarty F. E., Feighery C., Doherty D. G. 2001; Selective expansion and partial activation of human NK cells and NK receptor-positive T cells by IL-2 and IL-15. J Immunol 167:3129–3138 [CrossRef]
     [Google Scholar]
  14. Edwards B. H., Bansal A., Sabbaj S., Bakari J., Mulligan M. J., Goepfert P. A. 2002; Magnitude of functional CD8+ T-cell responses to the gag protein of human immunodeficiency virus type 1 correlates inversely with viral load in plasma. J Virol 76:2298–2305 [CrossRef]
     [Google Scholar]
  15. Fehniger T. A., Shah M. H., Turner M. J., VanDeusen J. B., Whitman S. P., Copper M. A., Suzuki K., Wechser M., Goodsaid F., Caligiuri M. A. 1999; Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response. J Immunol 162:4511–4520
     [Google Scholar]
  16. Ferlazzo G., Pack M., Thomas D., Paludan C., Schmid D., Strowig T., Bougras G., Muller W. A., Moretta L., Munz C. 2004; Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci U S A 101:16606–16611 [CrossRef]
     [Google Scholar]
  17. Gonzalez E., Kulkarni H., Bolivar H., Mangano A., Sanchez R., Catano G., Nibbs R. J., Freedman B. I., Quinones M. P. other authors 2005; The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307:1434–1440 [CrossRef]
     [Google Scholar]
  18. Gougeon M. L., Garcia S., Heeney J., Tschopp R., Lecoeur H., Guetard D., Rame V., Dauguet C., Montagnier L. 1993; Programmed cell death in AIDS-related HIV and SIV infections. AIDS Res Hum Retroviruses 9:553–563 [CrossRef]
     [Google Scholar]
  19. Grabstein K. H., Eisenman J., Shanebeck K., Rauch C., Srinivasan S., Fung V., Beers C., Richardson J., Schoenborn M. A. other authors 1994; Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor. Science 264:965–968 [CrossRef]
     [Google Scholar]
  20. Heeney J., Jonker R., Koornstra W., Dubbes R., Niphuis H., Di Rienzo A. M., Gougeon M. L., Montagnier L. 1993; The resistance of HIV-infected chimpanzees to progression to AIDS correlates with absence of HIV-related T-cell dysfunction. J Med Primatol 22:194–200
     [Google Scholar]
  21. Ibegbu C., Brodie-Hill A., Kourtis A. P., Carter A., McClure H., Wei Chen Z., Nahmias A. J. 2001; Use of human CD3 monoclonal antibody for accurate CD4+ and CD8+ lymphocyte determinations in macaques: phenotypic characterization of the CD3− CD8+ cell subset. J Med Primatol 30:291–298 [CrossRef]
     [Google Scholar]
  22. Kennedy M. K., Glaccum M., Brown S. N., Butz E. A., Viney J. L., Embers M., Matsuki N., Charrier K., Sedger L. other authors 2000; Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191:771–780 [CrossRef]
     [Google Scholar]
  23. Kestens L., Vingerhoets J., Peeters M., Vanham G., Vereecken C., Penne G., Niphuis H., van Eerd P., van der Groen G. other authors 1995; Phenotypic and functional parameters of cellular immunity in a chimpanzee with a naturally acquired simian immunodeficiency virus infection. J Infect Dis 172:957–963 [CrossRef]
     [Google Scholar]
  24. Kottilil S., Chun T. W., Moir S., Liu S., McLaughlin M., Hallahan C. W., Maldarelli F., Corey L., Fauci A. S. 2003; Innate immunity in human immunodeficiency virus infection: effect of viremia on natural killer cell function. J Infect Dis 187:1038–1045 [CrossRef]
     [Google Scholar]
  25. Kuniyoshi J. S., Kuniyoshi C. J., Lim A. M., Wang F. Y., Bade E. R., Lau R., Thomas E. K., Weber J. S. 1999; Dendritic cell secretion of IL-15 is induced by recombinant huCD40LT and augments the stimulation of antigen-specific cytolytic T cells. Cell Immunol 193:48–58 [CrossRef]
     [Google Scholar]
  26. Lauw F. N., Dekkers P. E. P., te Velde A. A., Speelman P., Levi M., Kurimoto M., Hack C. E., van Deventer S. J. H., van der Poll T. 1999; Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees. J Infect Dis 179:646–652 [CrossRef]
     [Google Scholar]
  27. Lodolce J., Burkett P., Koka R., Boone D., Chien M., Chan F., Madonia M., Chai S., Ma A. 2002; Interleukin-15 and the regulation of lymphoid homeostasis. Mol Immunol 39:537–544 [CrossRef]
     [Google Scholar]
  28. Matano T., Shibata R., Siemon C., Connors M., Lane H. C., Martin M. A. 1998; Administration of an anti-CD8 monoclonal antibody interferes with the clearance of chimeric simian/human immunodeficiency virus during primary infections of rhesus macaques. J Virol 72:164–169
     [Google Scholar]
  29. Mueller Y. M., Petrovas C., Bojczuk P. M., Dimitriou I. D., Beer B., Silvera P., Villinger F., Cairns J. S., Gracely E. J. other authors 2005; Interleukin-15 increases effector memory CD8+ T cells and NK cells in simian immunodeficiency virus-infected macaques. J Virol 79:4877–4885 [CrossRef]
     [Google Scholar]
  30. Musso T., Calosso L., Zucca M., Millesimo M., Ravarino D., Giovarelli M., Malavasi F., Ponzi A. N., Paus R., Bulfone-Paus S. 1999; Human monocytes constitutively express membrane-bound, biologically active, and interferon-upregulated interleukin-15. Blood 93:3531–3539
     [Google Scholar]
  31. 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 [CrossRef]
     [Google Scholar]
  32. Nehete P. N., Schapiro S. F., Johnson P. C., Murthy K. K., Satterfield W. C., Sastry K. J. 1998; A synthetic peptide from the first conserved region in the envelope protein gp160 is a strong T-cell epitope in HIV-infected chimpanzees and humans. Viral Immunol 11:147–158 [CrossRef]
     [Google Scholar]
  33. Neri S., Mariani E., Meneghetti A., Cattini L., Facchini A. 2001; Calcein-acetyoxymethyl cytotoxicity assay: standardization of a method allowing additional analyses on recovered effector cells and supernatants. Clin Diagn Lab Immunol 8:1131–1135
     [Google Scholar]
  34. Novembre F. J., Saucier M., Anderson D. C., Klumpp S. A., O'Neil S. P., Brown C. R., Hart C. E., Guenthner P. C., Swenson R. B., McClure H. M. 1997; Development of AIDS in a chimpanzee infected with human immunodeficiency virus type 1. J Virol 71:4086–4091
     [Google Scholar]
  35. Obata-Onai A., Hashimoto S., Onai N., Kurachi M., Nagai S., Shizuno K., Nagahata T., Matsushima K. 2002; Comprehensive gene expression analysis of human NK cells and CD8+ T lymphocytes. Int Immunol 14:1085–1098 [CrossRef]
     [Google Scholar]
  36. Ogg G. S., Kostense S., Klein M. R., Jurriaans S., Hamann D., McMichael A. J., Miedema F. 1999; Longitudinal phenotypic analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes: correlation with disease progression. J Virol 73:9153–9160
     [Google Scholar]
  37. Ohteki T., Suzue K., Maki C., Ota T., Koyasu S. 2001; Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response. Nat Immunol 2:1138–1143 [CrossRef]
     [Google Scholar]
  38. Ondoa P., Vingerhoets J., Vereecken C., Van Der Groen G., Heeney J. L., Kestens L. 2002; In vitro replication of SIVcpz is suppressed by β -chemokines and CD8+ T cells but not by natural killer cells of infected chimpanzees. AIDS Res Hum Retroviruses 18:373–382 [CrossRef]
     [Google Scholar]
  39. Ondoa P., Vereecken C., Fransen K., Colebunders R., van der Groen G., Heeney J. L., Kestens L. 2003; Human and simian immunodeficiency virus-infected chimpanzees do not have increased intracellular levels of β -chemokines in contrast to infected humans. J Med Virol 69:297–305 [CrossRef]
     [Google Scholar]
  40. O'Neil S. P., Novembre F. J., Hill A. B., Suwyn C., Hart C. E., Evans-Strickfaden T., Anderson D. C., deRosayro J., Herndon J. G. other authors 2000; Progressive infection in a subset of HIV-1 positive chimpanzees. J Infect Dis 182:1051–1062 [CrossRef]
     [Google Scholar]
  41. Palmer S., Wiegand A. P., Maldarelli F., Bazmi H., Mican J. M., Polis M., Dewar R. L., Planta A., Liu S. other authors 2003; New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 41:4531–4536 [CrossRef]
     [Google Scholar]
  42. Pien G. C., Satoskar A. R., Takeda K., Akira S., Biron C. A. 2000; Selective IL-18 requirements for induction of compartmental IFN- γ responses during viral infection. J Immunol 165:4787–4791 [CrossRef]
     [Google Scholar]
  43. Ranson T., Vosshenrich C. A., Corcuff E., Richard O., Laloux V., Lehuen A., Di Santo J. P. 2003; IL-15 is an essential mediator of peripheral NK-cell homeostasis. Blood 101:4887–4893 [CrossRef]
     [Google Scholar]
  44. Sanders-Buell E., Salminen M. O., McCutchan F. E. 1995 Sequencing primers for HIV-1 Rockville, MD: Henry M. Jackson Foundation Research Laboratory and Division of Retrovirology, Walter Reed Army Institute of Research; http://hiv-web.lanl.gov/content/hiv-db/COMPENDIUM/1995/PART-III/3.pdf
     [Google Scholar]
  45. Schmidt K. N., Leung B., Kwong M., Zarember K. A., Satyal S., Navas T. A., Wang F., Godowski P. J. 2004; APC-independent activation of NK cells by the toll-like receptor 3 agonist double-stranded RNA. J Immunol 172:138–143 [CrossRef]
     [Google Scholar]
  46. Shu U., Kiniwa M., Wu C. Y., Maliszewski C., Vezzio N., Hakimi J., Gately M., Delespesse G. 1995; Activated T cells induce interleukin-12 production by monocytes via CD40−CD40 ligand interaction. Eur J Immunol 25:1125–1128 [CrossRef]
     [Google Scholar]
  47. Siren J., Sareneva T., Pirhonen J., Strengell M., Veckman V., Julkunen I., Matikainen S. 2004; Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages. J Gen Virol 85:2357–2364 [CrossRef]
     [Google Scholar]
  48. Skov S., Bonyhadi M., Odum N., Ledbetter J. A. 2000; IL-2 and IL-15 regulate CD154 expression on activated CD4 T cells. J Immunol 164:3500–3505 [CrossRef]
     [Google Scholar]
  49. Strengell M., Matikainen S., Siren J., Lehtonen A., Foster D., Julkunen I., Sareneva T. 2003; IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells. J Immunol 170:5464–5469 [CrossRef]
     [Google Scholar]
  50. ten Haaft P., Murthy K., Salas M., McClure H., Dubbes R., Koornstra W., Niphuis H., Davis D., van der Groen G., Heeney J. 2001; Differences in early virus loads with different phenotypic variants of HIV-1 and SIVcpz in chimpanzees. AIDS 15:2085–2092 [CrossRef]
     [Google Scholar]
  51. Vankayalapati R., Kulcar P., Wizel B., Weis S. E., Samten B., Safi H., Shams H., Barnes P. F. 2004; NK cells regulate CD8+ T cell effector function in response to an intracellular pathogen. J Immunol 172:130–137 [CrossRef]
     [Google Scholar]
  52. Vitale M., Caruso A., Licenziati S., Rodella L., Fiorentini S., Zauli G., Castelli F., Manzoli F. A., Turano A. 2000; Differential production of IFN- γ , analyzed at the single-cell level, by specific subsets of human NK and T cells from healthy and HIV+ subjects. Cytometry 39:189–194 [CrossRef]
     [Google Scholar]
  53. Voevodin A., Samilchuk E., Dashti S. 1998; A survey for 32 nucleotide deletion in the CCR-5 chemokine receptor gene (deltaccr-5) conferring resistance to human immunodeficiency virus type 1 in different ethnic groups and in chimpanzees. J Med Virol 55:147–151 [CrossRef]
     [Google Scholar]
  54. Waldmann T. A., Tagaya Y. 1999; The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu Rev Immunol 17:19–49 [CrossRef]
     [Google Scholar]
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Influence of interleukin-15 on CD8+ natural killer cells in human immunodeficiency virus type 1-infected chimpanzees
J. Gen. Virol. 88, 641 (2007); https://doi.org/10.1099/vir.0.82154-0
/content/journal/jgv/10.1099/vir.0.82154-0
/content/journal/jgv/10.1099/vir.0.82154-0
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