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

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.

BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties

“…32 The ability of the CD8 C BTLA C subset to produce more IL-2 could therefore endow them with the preferential ability to expand and persist in vivo after infusion into patients.…”

Human Bone Marrow Hosts Polyfunctional Memory CD4+ and CD8+ T Cells with Close Contact to IL-15–Producing Cells

“…Analysis of the raw data was performed applying the GeneScan 3.7 analysis software package (Applied Biosystems) using the Local Southern method for fragment size estimation. The frequency of polyclonal, oligoclonal, and monoclonal profiles within the 24 Vb regions from paired BM and PB T cells from five donors was quantified based on deviations from the Gaussian distribution as described previously (14).…”

“…Quantitative RT-PCR experiments were performed using the LightCycler 480 System (Roche Diagnostics), 23 SYBR Green 1 Master (Roche Diagnostics), and GAPDH and b-actin as housekeeping genes for relative quantification of candidate genes as described previously (11). Sequence-specific oligonucleotide primers were designed using Primer3 software (12) TCR Vb CDR3 spectratype analysis TCR Vb transcripts of PBMC and BMMC were amplified by PCR using a HotStarTaq Master Mix Kit (Qiagen) and primers (MWG Biotech) specific for each of the human Vb families and a specific primer for the C region of the b-chain (labeled with fluorescein) as previously described (13,14). An aliquot of the PCR product was diluted in 20 ml formamide and 1.2 fmol internal lane standard GeneScan-500 LIZ (Applied Biosystems).…”

Innate Immune Responses in the Geriatric Population

“…As previously mentioned, it has been reported that IL-4 producing T cells with a CD25+ memory phenotype accumulate in a subgroup of healthy elderly people who have an intact humoral immune response after influenza vaccination. These apparently beneficial CD8+ CD25+ T cells are rare or even absent in older persons with latent CMV infection (Herndler-Brandstetter et al, 2005).…”

“…They produce IL-2 and IL-4, assist B memory generation, induce MHC II upregulation on B cells, and promote antibody isotype switching to IgG1 and IgE. These T cells coexpress CD4 molecule and present a highly diverse TCR repertoire and longer telomere compared to the CD8+ CD25-subset (Herndler-Brandstetter et al, 2005).…”