Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-12-9
pubmed:abstractText
Natural killer (NK) cells are an important subset of lymphocytes capable of killing virus-infected target cells without prior sensitization. HIV-infected individuals show impairment of their NK cell activity. Although the mechanism responsible for this defect remains unclear, NK cytotoxicity of lymphocytes from these individuals can be partially restored by interleukin (IL)-2. IL-15 is a recently discovered cytokine that shares many biologic activities with IL-2--for example, enhancement of NK activity. In this study, we investigated the effect of recombinant IL-15 (rIL-15) on the NK and antibody-dependent cellular cytotoxicity (ADCC) effector activities of peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals using K562 cell line and HIV gp120-expressing cells. The effect of anti-IL-15 antibodies on NK activity was also examined using PBMCs of HIV-seronegative individuals. Our results show that NK and ADCC activities of PBMCs in HIV-seropositive patients were significantly lower than those of seronegative donors (p < or = 0.05). However, these two activities were significantly enhanced when rIL-15 was added to the assay wells (p < or = 0.05). Moreover, addition of saturating concentrations of neutralizing monoclonal antibodies (mAb) specific for IL-2, IL-12, or interferon (IFN)-gamma in the assays failed to inhibit IL-15-mediated enhancement of NK cell functions. Only the antibody against IL-15 abrogated the upregulation of NK and ADCC activities mediated by IL-15, suggesting that this cytokine enhances NK cell functions through a mechanism that is independent of the induction of other cytokines. IL-15 did not exert any modulatory effect on the expression of CD16 or CD56 molecules. Our results show that IL-15 can increase the NK and ADCC activities of the PBMCs of HIV-infected individuals in vitro. In view of its higher therapeutic index as determined using murine models, IL-15 may represent a better immunotherapeutic agent than IL-2 to restore these functions in HIV-seropositive patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1077-9450
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
137-45
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Enhancement of natural killer and antibody-dependent cytolytic activities of the peripheral blood mononuclear cells of HIV-infected patients by recombinant IL-15.
pubmed:affiliation
Department of Microbiology and Immunology, University of Montreal and Ste-Justine Hospital, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't