MOAA0101 - Oral Abstract Session
Differential impact of IL-7 and IL-15 on HIV reservoir persistence
Presented by Claire Vandergeeten (United States).
C. Vandergeeten1, S. Da Fonseca1, I. Sereti2, M. Lederman3, R.-P. Sekaly1, N. Chomont1
1Vaccine and Gene Therapy Institute, Port St Lucie, United States, 2NIAID, Bethesda, United States, 3Case Western University, Cleveland, United States
Background: A small pool of
long-lived latently infected CD4 T-cells is the major obstacle to HIV
eradication. gc-cytokines such
as IL-7 and IL-15 contribute to the maintenance of memory CD4 T-cells by
promoting their survival and proliferation. The relative impact of these
cytokines on the maintenance of latently infected CD4 T cells during
suppressive HAART is unknown.
Methods: To characterize
the effect of IL-7 and IL-15 in vitro, we
exposed CD4 T-cells from HAART-treated subjects to IL-7 and IL-15 in the
presence of antiretrovirals. After 6 days, supernatants were collected to
measure viral reactivation by RT-PCR. We evaluated the pro-differential effect
of these gc-cytokines in the presence of
autologous monocytes by flow cytometry. We also measured the expression of
activation markers on CD4 T-cell. Finally, we quantified HIV DNA in CD4 T-cells
obtained from HAART-treated subjects receiving IL-7 by real-time PCR.
Results: IL-15 induced
viral production in latently infected cells very efficiently when compared to
IL-7. Moreover, IL-15 increased the percentage of TEM cells in
monocytes cocultures. The percentage of CD4 T-cells expressing Ki67 after 9
days of culture revealed that IL-7 is a potent inducer of CD4 T-cells
proliferation compared to IL-15. IL-15 promoted preferentially the
proliferation of TEM and TTM while IL-7 induced
proliferation of TN and TCM. Finally, we observed an
increase in the frequency of CD4 T-cells harboring HIV integrated DNA upon IL-7
treatment in HAART-treated subjects.
Conclusion: Our results
indicate that IL-7 maintains the reservoir by inducing homeostatic
proliferation of cells harboring integrated DNA with minimal effect on HIV
reactivation both in vitro and in vivo. IL-15 induces viral reactivation in vitro as a consequence of differentiation of memory CD4 T-cells with a
minimal effect on proliferation. Our results suggest that IL-15 therapy may be
used as a strategy to deplete the latent HIV reservoir.
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