Affiliations: School of Pathology and Laboratory Medicine,
University of Western Australia and PathWest Laboratory Medicine, Perth,
Australia | Department of Clinical Immunology, Royal Perth
Hospital and PathWest Laboratory Medicine, Perth, Australia
Note: [] Corresponding author: Dr. Sonia Fernandez, School of Pathology
and Laboratory Medicine, University of Western Australia, Level 2, MRF
Building, Rear 50 Murray St, Perth WA 6001, Australia. Tel.: +61 8 92240223;
Fax: +61 8 92240204; E-mail: sonia.fernandez@uwa.edu.au
Abstract: HIV-infected individuals responding to antiretroviral therapy (ART)
after severe CD4^{+} T-cell depletion may retain low
responses to recall antigens [eg: cytomegalovirus (CMV)] and altered expression
of T-cell co-stimulatory molecules consistent with immunosenescence. We
investigated the capacity of phenotypically senescent cells to generate
cytokines in HIV patients receiving long-term ART (n=18)
and in healthy controls (n=10). Memory T-cells were
assessed by interferon (IFN)-γ ELISpot assay and flow
cytometrically via IFN-γ or IL-2. Proportions of
CD57^{bright}CD28^{null}
CD4^{+} T-cells correlated with IFN-γ responses to CMV (p=0.009) and anti-CD3
(p=0.002) in HIV patients only. Proportions of
CD57^{bright}CD28^{null}
CD8^{+} T-cells and CD8^{+} T-cell
IFN-γ responses to CMV peptides correlated in controls
but not HIV patients. IL-2 was predominantly produced by
CD28^{+}T-cells from all donors, whereas IFN-γ was mostly produced by CD57^{+} T-cells. The
findings provide evidence of an accumulation of immunosenescent T-cells able to
make IFN-γ. This may influence the pathogenesis of
secondary viral infections in HIV patients receiving ART.
