Interleukin-15 enhances the secretion of IFN-gamma and CC chemokines by natural killer cells from HIV viremic and aviremic patients.
Several lines of evidence documented a renewed interest in the role of natural killer (NK) cells in the innate immune control of HIV infection and disease progression. To further assess the role of NK cells as target for immunotherapy in HIV infection, we evaluated the priming effect of interleukin (IL)-15 on freshly isolated human peripheral NK cells, from viremic and aviremic HIV-infected patients, measuring the production of IFN-gamma and CC chemokines. In vitro IL-15 priming induced a significant increase of IFN-gamma production in both viremic and aviremic patients. IL-15 stimulated NK cells producing CC chemokine quantities that are reported to be capable of inhibiting HIV infection and replication. This priming effect is observed both in viral suppressed patients after antiretroviral therapy, and in viremic subjects with progressive HIV infection. The combination of IL-15 plus IL-12 is the most potent costimulus for CD69 expression and production of CC chemokines by NK cells. These findings indicate that NK cells are an important target for immunotherapeutic agents and provide additional pre-clinical data supporting the great potential of IL-15 in the immune-based interventions in HIV disease.
d'Ettorre
Gabriella
G
Department of Infectious and Tropical Diseases, La Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy.
Andreotti
Mauro
M
Carnevalini
Martina
M
Andreoni
Carolina
C
Zaffiri
Lorenzo
L
Vullo
Vincenzo
V
Vella
Stefano
S
Mastroianni
Claudio M
CM
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D054407:Chemokine CCL4 / Q000096:biosynthesis / Q000235:genetics; D019742:Chemokines, CC / Q000378:metabolism*; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D019409:Interleukin-15 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D014766:Viremia / Q000378:metabolism*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D054407:Chemokine CCL4; D019742:Chemokines, CC; D007371:Interferon-gamma; D019409:Interleukin-15; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C066507:CCL4 protein, human