Memory T Cells Constitute a Subset of the Human CD8+CD45RA+ Pool with Distinct Phenotypic and Migratory Characteristics

• Published in: The Journal of immunology (1950) Vol. 167; no. 1; pp. 212 - 220
• Main Authors: Faint, Jeffery M, Annels, Nicola E, Curnow, S. John, Shields, Philip, Pilling, Darrell, Hislop, Andrew D, Wu, Lijun, Akbar, Arne N, Buckley, Christopher D, Moss, Paul A. H, Adams, David H, Rickinson, Alan B, Salmon, Mike
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-07-2001
• Subjects: Apoptosis - immunology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Division - immunology; Cell Movement - immunology; Chemotaxis, Leukocyte - immunology; Epitopes, T-Lymphocyte - metabolism; HLA-A2 Antigen - metabolism; HLA-B8 Antigen - metabolism; Humans; Immunologic Memory; Immunophenotyping; Interphase - immunology; Leukocyte Common Antigens - biosynthesis; Lymphocyte Function-Associated Antigen-1 - biosynthesis; Organ Specificity - immunology; Peptide Fragments - immunology; Peptide Fragments - metabolism; Receptors, CCR5 - biosynthesis; Receptors, CCR7; Receptors, Chemokine - biosynthesis; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.1.212

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.