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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2003-02-0420.
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Blood, 1 September 2003, Vol. 102, No. 5, pp. 1779-1787
IMMUNOBIOLOGY
Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions
Nathalie Rufer,
Alfred Zippelius,
Pascal Batard,
Mikaël J. Pittet,
Isabel Kurth,
Patricia Corthesy,
Jean-Charles Cerottini,
Serge Leyvraz,
Eddy Roosnek,
Markus Nabholz, and
Pedro Romero
From the Swiss Institute for Experimental Cancer Research, Epalinges,
Switzerland; Division of Clinical Onco-Immunology, Ludwig Institute for Cancer
Research, Lausanne Branch, University Hospital, Lausanne, Switzerland; Ludwig
Institute for Cancer Research, Lausanne Branch, University of Lausanne,
Epalinges, Switzerland; Multidisciplinary Oncology Center, University Hospital
(CHUV), Lausanne, Switzerland; and Division of Immunology and Allergology,
University Hospital of Geneva, Geneva, Switzerland.
After antigenic challenge, naive T lymphocytes enter a program of
proliferation and differentiation during the course of which they acquire
effector functions and may ultimately become memory cells. In humans, the
pathways of effector and memory T-cell differentiation remain poorly defined.
Here we describe the properties of 2 CD8+ T-lymphocyte subsets,
RA+CCR727+28+ and
RA+CCR727+28, in
human peripheral blood. These cells display phenotypic and functional features
that are intermediate between naive and effector T cells. Like naive T
lymphocytes, both subsets show relatively long telomeres. However, unlike the
naive population, these T cells exhibit reduced levels of T-cell receptor
excision circles (TRECs), indicating they have undergone additional rounds of
in vivo cell division. Furthermore, we show that they also share effector-type
properties. At equivalent in vivo replicative history, the 2 subsets express
high levels of Fas/CD95 and CD11a, as well as increasing levels of effector
mediators such as granzyme B, perforin, interferon , and tumor necrosis
factor . Both display partial ex vivo cytolytic activity and can be
found among cytomegalovirus-specific cytolytic T cells. Taken together, our
data point to the presence of T cells with intermediate effector-like
functions and suggest that these subsets consist of T lymphocytes that are
evolving toward a more differentiated effector or effector-memory stage.

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