Healthy Aging and Latent Infection with
CMV Lead to Distinct Changes in CD8
and CD4
T-Cell Subsets in the Elderly
Birgit Weinberger, Lutfan Lazuardi,
Ilka Weiskirchner, Michael Keller, Christoph Neuner,
Karl-Heinz Fischer, Ber Neuman, Reinhard Würzner,
and Beatrix Grubeck-Loebenstein
ABSTRACT: Despite general acceptance that immuno-
logic changes are associated with aging and latent in-
fection with Cytomegalovirus (CMV), no clear-cut
distinction has so far been made between strictly age-
related and CMV-induced changes. We therefore com-
pared CD4
+
and CD8
+
naïve (CD45RA+CD28+),
memory (CD45RA-CD28+), and effector (CD28
-
)T
cells in CMV-positive (n = 164) and CMV-negative (n
= 87) elderly persons and correlated CD8
+
and CD4
+
effector T cells with other T-cell subpopulations. Per-
centages of CD8
+
as well as CD4
+
effector T cells were
higher, but percentages of naïve and memory cells were
lower in CMV-positive compared to CMV-negative el-
derly persons. Negative correlations within CD8
+
T-
cell subsets were found to be present in both CMV-
positive and CMV-negative elderly individuals. In
contrast, correlations within CD4
+
T-cell subpopulations
and a positive correlation between CD8
+
and CD4
+
effec-
tor T cells were found in CMV-positive individuals only.
Our results demonstrate that (a) in the elderly different
T-cell subsets compete for space within the CD8
+
, but not
the CD4
+
T-cell population; (b) CMV induces changes in
the CD4
+
compartment that differ from the solely age-
related changes seen in CMV-negative elderly population;
and (c) the CMV-status of a population has to be taken into
account before a conclusion on the effect of aging on the
composition of the T-cell pool can be reached. Human
Immunology 68, 86 –90 (2007). © American Society for
Histocompatibility and Immunogenetics, 2007. Published
by Elsevier Inc.
KEYWORDS: CMV; T-cell subsets; aging; CD8
+
;
CD4
+
ABBREVIATIONS
CMV Cytomegalovirus
CD cluster of differentiation
FACS fluorescence-activated cell sorting
IFN Interferon
INTRODUCTION
It is generally recognized that the function of the im-
mune system declines with age [1, 2] leading to in-
creased susceptibility to infectious disease and endanger-
ing the protective effect of vaccination [3, 4]. Because of
the involution of the thymus, changes in the composition
of the T-cell repertoire are among the most striking
features of immunosenescence. A decreased thymic out-
put of naïve T cells leads to low naïve T-cell numbers in
the peripheral blood as well as in the lymph node tissue,
whereas there is an increase in the numbers of memory
and effector T cells [5, 6]. These changes seem to be more
pronounced in the CD8
+
than in the CD4
+
T-cell pool.
Longitudinal studies suggest that decreased CD4
+
/CD8
+
ratios, together with increased numbers of CD57
+
and
CD28
-
T cells and poor T-cell proliferation are part of
the “immunologic risk phenotype” (IRP), which corre-
lates with subsequent 2-year mortality in the elderly
[7, 8]. The pronounced accumulation of CD28
-
CD57
-
effector cells that produce large amounts of IFN may
From the Immunology Division (B.W., L.L., I.W., M.K., B.G.-L.),
Institute for Biomedical Aging Research, Austrian Academy of Sciences,
Innsbruck, Austria, Department of Public Health (C.N. K.-H. F.), County
of Tyrol, Innsbruck, Austria, Department of Public Health (B.N.), Town-
ship of Innsbruck, Innsbruck, Austria, and Department of Hygiene (R.W.),
Microbiology and Social Medicine, Medical University, Innsbruck, Austria.
Address reprint requests to: Prof. Beatrix Grubeck-Loebenstein, Institute
for Biomedical Aging Research, Rennweg 10, 6020 Innsbruck, Austria;
Tel: +43-512-583919-10; Fax: +43-512-583919-8; Email: beatrix.
grubeck@oeaw.ac.at.
B.W. and L.L contributed equally to this paper.
Received August 18, 2006; revised October 16, 2006; accepted October
31, 2006.
Human Immunology 68, 86 –90 (2007)
© American Society for Histocompatibility and Immunogenetics, 2007 0198-8859/07/$–see front matter
Published by Elsevier Inc. doi:10.1016/j.humimm.2006.10.019