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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 {gamma}, and tumor necrosis factor {alpha}. 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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