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CD25-Expressing CD8+ T Cells Are Potent Memory Cells in Old Age

2005; American Association of Immunologists; Volume: 175; Issue: 3 Linguagem: Inglês

10.4049/jimmunol.175.3.1566

1550-6606

Dietmar Herndler‐Brandstetter, Susanne Schwaiger, Ellen Veel, Christine Fehrer, Daniel Cioca, Giovanni Almanzar, Michael Keller, Gerald Pfister, Walther Parson, Reinhard Würzner, Diether Schönitzer, Siân M. Henson, Richard Aspinall, Günter Lepperdinger, Beatrix Grubeck‐Loebenstein,

CAR-T cell therapy research

Abstract We have recently described an IL-2/IL-4-producing CD8+CD25+ nonregulatory memory T cell population that occurs in a subgroup of healthy elderly persons who characteristically still have a good humoral response after vaccination. The present study addresses this specific T cell subset and investigates its origin, clonal composition, Ag specificity, and replicative history. We demonstrate that CD8+CD25+ memory T cells frequently exhibit a CD4+CD8+ double-positive phenotype. The expression of the CD8 αβ molecule and the occurrence of signal-joint TCR rearrangement excision circles suggest a thymic origin of these cells. They also have longer telomeres than their CD8+CD25− memory counterparts, thus indicating a shorter replicative history. CD8+CD25+ memory T cells display a polyclonal TCR repertoire and respond to IL-2 as well as to a panel of different Ags, whereas the CD8+CD25− memory T cell population has a more restricted TCR diversity, responds to fewer Ags, and does not proliferate in response to stimulation with IL-2. Molecular tracking of specific clones with clonotypic primers reveals that the same clones occur in CD8+CD25+ and CD8+CD25− memory T cell populations, demonstrating a lineage relationship between CD25+ and CD25− memory CD8+ T cells. Our results suggest that CD25-expressing memory T cells represent an early stage in the differentiation of CD8+ cells. Accumulation of these cells in elderly persons appears to be a prerequisite of intact immune responsiveness in the absence of naive T cells in old age.