Memory T cells constitute a subset of the human CD8+CD45RA+ pool with distinct phenotypic and migratory characteristics.
Using HLA class I-viral epitope tetramers to monitor herpes virus-specific CD8(+) T cell responses in humans, we have shown that a significant fraction of responding cells revert from a CD45RO(+) to a CD45RA(+) state after priming. All tetramer-binding CD45RA(+) cells, regardless of epitope specificity, expressed a phenotype LFA-1(high)CCR7(low) that was stable for at least 10 years in infectious mononucleosis patients and indefinitely in asymptomatic carriers. CD8(+)CD45RA(+)LFA-1(high) cells were not present in cord blood but in adults account for up to 50% of CD8(+)CD45RA(+) cells. These CD45RA(+)LFA-1(high) cells have significantly shorter telomeres than CD45RA(+)LFA-1(low) cells, suggesting that the latter represent a naive population, while the former are memory cells. CD45RA(+) memory cells are a stable population of noncycling cells, but on stimulation they are potent producers of IFN-gamma, while naive CD8(+) cells produce only IL-2. The chemokine receptor profile and migratory potential of CD45RA(+) memory cells is very similar to CD45RO(+) cells but different to naive CD8 cells. In accord with this, CD45RA(+) memory cells were significantly underrepresented in lymph nodes, but account for virtually all CD8(+)CD45RA(+) T cells in peripheral tissues of the same individuals.
Faint
J M
JM
University of Birmingham/Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom.
Annels
N E
NE
Curnow
S J
SJ
Shields
P
P
Pilling
D
D
Hislop
A D
AD
Wu
L
L
Akbar
A N
AN
Buckley
C D
CD
Moss
P A
PA
Adams
D H
DH
Rickinson
A B
AB
Salmon
M
M
D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism; D015795:HLA-B8 Antigen / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D009928:Organ Specificity / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D019713:Receptors, CCR5 / Q000096:biosynthesis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
C515370:CCR7 protein, human; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015795:HLA-B8 Antigen; D016169:Lymphocyte Function-Associated Antigen-1; D010446:Peptide Fragments; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens