Memory T Cells Constitute a Subset of the Human CD8+ CD45RA+ Pool With Distinct Phenotypic and Migratory Characteristics (original) (raw)
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-␥, 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.
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Circulating CD4 + CD8 + T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4 + CD8 + T cells in rhesus macaques. Two distinct populations of CD4 + CD8 + T cells were identified: the dominant one was CD4 hi CD8 lo and expressed the CD8aa homodimer, while the minor population was CD4 lo CD8 hi and expressed the CD8ab heterodimer. The majority of CD4 hi CD8a lo T cells exhibited an activated effector/memory phenotype (CCR5 lo CD7-CD28-HLA-DR +) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4 hi CD8a lo T cells compared to single-positive CD4 + T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4 hi CD8a lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4 hi CD8a lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4 + T cells expressing CD8a represent an effector/memory subset of CD4 + T cells and that this cell population can be depleted during the course of SIV infection.
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Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes
The Journal of Immunology, 2007
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