Maintenance and Attrition of T-Cell Memory

National Research Council Canada, Ottawa, Ontario, Canada
Critical Reviews in Immunology (Impact Factor: 3.7). 02/2003; 23(1-2):129-47. DOI: 10.1615/CritRevImmunol.v23.i12.70
Source: PubMed


After antigenic stimulation in the context of "danger signals," naive T cells embark on a programmed, intense expansion phase to counteract the rapid proliferation of pathogens. During the first week of infection, responding T cells undergo > 1000-fold expansion, resulting in the development of large numbers of cells exhibiting potent effector function. As the pathogen (antigen) burden dwindles, a majority of the effectors generated are eliminated by apoptosis, resulting in the survival and maintenance of a small population of antigen-specific cells as long-term memory T cells. Depending on the infection studied, CD8+ T cells appear to differentiate through multiple pathways into resting and effector memory subsets, and require multiple cytokines and cell surface molecules for survival and proliferation. Once generated, the repertoire of memory T cells remains highly vulnerable to attrition during heterologous infections, where homeostatic forces drive deletions in T-cell memory pools to accommodate the entry of new memory T cells. This review will primarily focus on the factors that influence the generation, maintenance, and attrition of memory CD8+ T cells.

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    • "Furthermore, adoptive transfer therapies involving tumor-antigen specific CD8+ T cells have shown cancer regression in clinical trials [1]. Moreover, memory CD8+ T cells can vary in both magnitude and quality [7]–[9] and generating a central memory population with a high level expression of CD62L (TCM) yields longer lasting tumor regression compared to CD62L low effector memory cells (TEM) [10]–[12]. We have previously reported that the choice of vaccine adjuvant and/or vector can also differentially impact the proportion of the two types of memory CD8+ T cells; for example Listeria monocytogenes generates a predominant CD62Lhigh central memory cells [13]. "
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    ABSTRACT: Central memory CD8(+) T cells expressing the adhesion molecule CD62L (L-selectin) are potent mediators of anti-cancer immunity due to their ability to proliferate extensively upon antigen re-stimulation. The interaction of selectin with its ligands mediates leukocyte rolling along high endothelial venules. Mice deficient in α(1,3) Fucosyltransferase IV and VII (FtDKO) lack functional L, P and E selectin ligands. Thus, we addressed whether the lack of selectin ligand interactions alters tumor protection by CD8(+) T cells in FtDKO mice. Listeria monocytogenes-OVA (LM-OVA) infection evoked potent OVA-specific CD8(+) T cells that proliferated and contracted at similar kinetics and phenotype in FtDKO and wild-type mice. Additionally, OVA-specific CD8(+) T cells in both mouse strains exhibited similar phenotypic differentiation, in vivo cytolytic activity and IFN-γ expression. However, FtDKO mice succumbed to B16-OVA tumors significantly earlier than wild-type mice. In contrast, FtDKO mice evoked strong recall memory CD8(+) T cell responses and protection to systemic LM-OVA re-challenge. The diminished tumor protection in FtDKO mice was not related to defective antigen presentation by dendritic cells or reduced proliferation of antigen-specific CD8(+) T cells. However, WT or FtDKO OVA-specific CD8(+) T cells showed significantly reduced ability to traffic to lymph nodes upon adoptive transfer into naïve FtDKO recipients. Furthermore, FtDKO OVA-specific CD8(+) T cells displayed poor ability to infiltrate tumors growing in WT mice. These results reveal that selectin ligand expression on host endothelium as well CD8(+) T cells may be important for their efficient and continued extravasation into peripheral tumors.
    PLoS ONE 02/2012; 7(2):e32211. DOI:10.1371/journal.pone.0032211 · 3.23 Impact Factor
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    ABSTRACT: Ozone, the principal oxidant pollutant in photochemical smog, causes airway epithelial injury in the upper and lower respiratory tract of laboratory animals. We have recently reported that long-term inhalation exposure to ozone causes mucous-cell metaplasia (MCM) in the surface epithelium lining the nasal airways of F344 rats. The principal objective of the present study was to determine the persistence of ozone-induced MCM in the nasal epithelium after the end of a chronic exposure. Male F344/N rats were exposed to 0, 0.25, or 0.5 ppm ozone, for 8 h/d, 7 d/wk for 13 wk. Animals were killed 8 h, 4 wk, or 13 wk after the end of the chronic exposure. Ozone-related alterations in the nasal epithelium were qualitatively and quantitatively characterized through histochemistry, image analysis, and morphometric techniques. Some rats were exposed for an additional 8 h to 0.5 ppm ozone at 13 wk after the end of the chronic exposure to determine whether previous ozone exposure results in persistent changes in the sensitivity of nasal epithelium to acute injury. At the end of the chronic exposure, hyperplasia was present in the nasal epithelium of rats exposed to 0.25 and 0.5 ppm ozone. By 13 wk postexposure, this proliferative alteration was still evident only in the rats exposed to 0.5 ppm ozone. Ozone-induced MCM with associated intraepithelial mucosubstances was evident only in the nasal tissues of rats exposed to 0.5 ppm ozone. Though attenuated, these alterations in the nasal mucous apparatus were still detectable at 13 wk after the end of the exposure. At this same time after the chronic exposure, an acute (8 h) exposure to 0.5 ppm ozone induced an additional increase of mucosubstances in the nasal epithelium of rats previously exposed to 0.5 ppm ozone, but not in rats chronically exposed to 0 or 2.5 ppm ozone. The persistent nature of the ozone-induced MCM in rats documented in this report suggests that ozone exposure may have the potential to induce similar long-lasting alterations in the airways of humans.
    American Journal of Respiratory Cell and Molecular Biology 04/1999; 20(3):517-29. DOI:10.1165/ajrcmb.20.3.3227 · 3.99 Impact Factor
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