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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2003-02-0420.
Submitted February 7, 2003
Accepted April 29, 2003
Ex-vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions
Nathalie Rufer*, Alfred Zippelius, Pascal Batard, Mikael J Pittet, Isabel Kurth, Patricia Corthesy, Jean-Charles Cerottini, Serge Leyvraz, Eddy Roosnek, Markus Nabholz, and Pedro Romero
Swiss Insitute for Experimental Cancer Research, Epalinges, Switzerland; NCCR Molecular Oncology program of the Swiss National Science Foundation, Epalinges, Switzerland
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland
Lausanne Branch, Ludwig Institute for Cancer Research, Epalinges, Switzerland
Multidisciplinary Oncology Center, University Hospital (CHUV), Lausanne, Switzerland
Division of Immunology and Allergology, University Hospital of Geneva, Geneva, Switzerland
* Corresponding author; email: nathalie.rufer{at}isrec.unil.ch.
After antigenic challenge, naive T lymphocytes enter a program of proliferation and differentiation in 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 two CD8+ T-lymphocyte subsets, RA+CCR7-27+28+ and RA+CCR7-27+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 two subsets express high levels of Fas/CD95 and CD11a, as well as increasing levels of effector mediators such as granzyme B, perforin, IFN- and TNF- . Both display partial ex-vivo cytolytic activity and can be found among CMV-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 towards a more differentiated effector and/or effector-memory stage.
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