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

Abstract

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-1highCCR7low that was stable for at least 10 years in infectious mononucleosis patients and indefinitely in asymptomatic carriers. CD8+CD45RA+LFA-1high cells were not present in cord blood but in adults account for up to 50% of CD8+CD45RA+ cells. These CD45RA+LFA-1high cells have significantly shorter telomeres than CD45RA+LFA-1low 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-γ, 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.

CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow

“…In addition we used in vivo-activated lymphocytes, which are L-selectin-negative and LFA-1 high when compared with blood lymphocytes. 46 Inhibition of CXCR3 reduced adhesion to TNF-␣/IFN-␥-stimulated HSECs under flow in all conditions by ϳ50%. The level of inhibition was similar to that seen using the global Gpi inhibitor pertussis toxin suggesting that most of the chemokine-mediated effect in this system was through CXCR3.…”

Functional impairment of human T-lymphocytes following PHA-induced expansion and retroviral transduction: implications for gene therapy

“…The nature of the cells that mediate the different facets of T cell-dependent immune function has remained largely undefined. [17][18][19][20][21] Functional characterisation of T-lymphocytes has recently been shown by Sallusto et al 22 on the basis of their expression of the chemokine receptor CCR7 and the memory marker CD45RA. CCR7 Ϫ /CD45RA Ϫ effector memory T (T EM ) cells display an immediate effector functional profile including cytolytic capacity and expression of the cytotoxic mediator perforin.…”

“…[17][18][19][20][21] Combined analysis of CD45RA and CCR7 expression has recently enabled improved characterization of T cell functional subsets. 22,23 Our results showed marked differences between polyclonal stimulation with PHA and iCD3/iCD28 with regard to the functional outcome of the expanded T-lymphocytes, and in particular to their expression of functional markers, such as perforin.…”

Ex Vivo Priming of Naïve T Cells Into EBV-Specific Th1/Tc1 Effector Cells by Mature Autologous DC Loaded with Apoptotic/Necrotic LCL

“…These responders were most likely the CD45RO+/CD62L-effector memory cells (20,21,26). In contrast, the CD45RO+/CD62L+ CTLs, also known as the central memory T cells, were most likely unable to respond in our assays, as previously described (20,21,26,27). However the presence of both types of 'effectors' in the resulting CTL lines is desirable and may strengthen the clinical efficacy of cellular immunotherapies, as it will allow for each subset to contribute to protective antiviral immunity and memory T-cell survival (20,21,28).…”