Influence of interleukin-15 on CD8+ natural killer cells in human immunodeficiency virus type 1-infected chimpanzees.
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-gamma) production was evaluated in naive and HIV-1-infected chimpanzees. In vitro stimulation of whole-blood cultures with recombinant gp120 (rgp120) resulted in enhanced IFN-gamma production predominantly by the CD3(-) CD8(+) subset of NK cells, and addition of anti-IL-15 to the system decreased IFN-gamma production. Moreover, in vitro stimulation with recombinant IL-15 (rIL-15) augmented IFN-gamma 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-gamma, and that IL-15 elicits IFN-gamma production in this subpopulation of NK cells in HIV-1-infected chimpanzees.
Rodriguez
Annette R
AR
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA.|Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
Arulanandam
Bernard P
BP
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA.
Hodara
Vida L
VL
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
McClure
Hazel M
HM
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
Cobb
Elaine K
EK
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
Salas
Mary T
MT
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
White
Robert
R
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
Murthy
Krishna K
KK
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism*; D002908:Chronic Disease; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002679:Pan troglodytes; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D016827:CD8 Antigens; D019409:Interleukin-15; D012367:RNA, Viral; D007371:Interferon-gamma