CD25-expressing CD8+ T cells are potent memory cells in old age.
We have recently described an IL-2/IL-4-producing CD8+CD25+ non-regulatory 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 alphabeta 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.
Herndler-Brandstetter
Dietmar
D
Immunology Division, Institute for Biomedical Aging and Research, Austrian Academy of Sciences, Innsbruck, Austria.
Schwaiger
Susanne
S
Veel
Ellen
E
Fehrer
Christine
C
Cioca
Daniel P
DP
Almanzar
Giovanni
G
Keller
Michael
M
Pfister
Gerald
G
Parson
Walther
W
Würzner
Reinhard
R
Schönitzer
Diether
D
Henson
Sian M
SM
Aspinall
Richard
R
Lepperdinger
Günter
G
Grubeck-Loebenstein
Beatrix
B
D000368:Aged; D000369:Aged, 80 and over; D015704:CD4 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007519:Isoantigens / Q000494:pharmacology; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2; D007519:Isoantigens; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019041:L-Selectin