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Interleukin-15 Enhances the Natural Killer Activity According to HAART Suppression of HIV-1 Replication
Mauro Andreotti*1, G d'Ettorre2, C Andreoni2, M Mancini1, S Antonucci2, M Giuliano1, S Vella1, V Vullo2, and C Mastroianni2
1Inst Superiore di Sanità, Rome, Italy and 2Univ La Sapienza, Rome Italy
Background: Natural killer (NK) cells are important effectors of innate immune
response with antiviral functions. Much evidence has been reported about NK frequency
and cytotoxicity impairment in HIV-infected subjects
and the partial normalization during HAART. In a previous study we reported the
decrease of production of interleukin-15 (IL-15) by peripheral
blood mononuclear cells (PBMC) in naive and in HAART-treated viremic patients. On the contrary, in patients who responded
to HAART, IL-15 production was comparable to that of healthy donors. In
the present study, we have evaluated the effect of exogenous IL-15 administration
on NK cytotoxicity in HAART-treated patients with suppressed
or detectable plasma RNA.
Methods: The study population comprised 17
HAART-treated patients with RNA <1.7 log (Group A); 13 HAART-treated viremic patients with 2.99 log median RNA (Group B), and 10
HIV-negative healthy donors (Group C). PBMC were cultured at concentrations of 2
x 106 cells/mL overnight with medium alone
and in the presence of recombinant IL-15 (10 ng/mL). Cultured
PBMC were tested for their lytic activity against 51Cr-labeled
K562 cells at different effector (E):target (T) ratios. Results are expressed like number of E
required to lyse the 20% of T cells contained in 107
E cells (LU/107). Statistical analysis was done by non-parametric
tests.
Results: NK cell cytolytic activity was increased by
IL-15 stimulation as well in Group B patients (medium = 24.5 LU/107;
medium+IL-15 = 125.8; p <0.0005)
as in Group A patients (medium = 27.8 LU/107; medium+IL-15 = 70.6; p <0.0005). No significant increase
was observed in Group C subjects. When we compared the ratios of LU/107
(medium+IL-15 LU/107 / medium LU/107) of HAART-treated
patients, we observed that IL-15 induced a stronger stimulation in Group B than
Group A (p <0.02). The table summarizes.
Conclusions: Our data suggest that IL-15 is capable of priming cytotolityc
activity of NK cells in HIV-infected patients during HAART, suggesting a
possible role in immune therapy. In particular, the observed high values of IL-15-primed
NK cells LU/107 in viremic HAART patients underline
the ability of IL-15 in abolishing the natural immune impairment despite HIV
replication.
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