Long-term persistence and reactivation of T cell memory in the lung of mice infected with respiratory syncytial virus

Ostler, Tobias; Hussell, Tracy; Surh, Charles D.; Openshaw, Peter; Ehl, Stephan

doi:10.1002/1521-4141(200109)31:9<2574::aid-immu2574>3.0.co;2-v

Cited by 86 publications

(71 citation statements)

References 23 publications

(12 reference statements)

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“…(ii) Impact of age on the early phases of the recall response Effector-memory CD8 + T cells persist in the lung airways of both humans and animals following resolution of a respiratory virus infection (de Bree et al, 2005;Hogan et al, 2001a;Ostler et al, 2001;van Panhuys et al, 2005;Wiley et al, 2001). There is substantial evidence that these cells play a key role in mediating the initial phase (phase 1) of the recall response to secondary infection.…”

Section: (I) Basic Features Of the Cd8 + T Cell Recall Response To Rementioning

confidence: 99%

Aging and CD8+ T cell immunity to respiratory virus infections

Ely

Roberts

Kohlmeier

et al. 2007

Experimental Gerontology

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The capacity of the immune system to mediate effective immune responses to pathogens declines with age. In the case of immune responses to newly encountered antigens, several studies have demonstrated that this decline reflects both a loss of naïve T cells and changes in the repertoire and function of these cells over time. However, comparatively little is known about the impact of age on established memory T cells pools. Here we discuss age-related changes in memory CD8 + T cell pools elicited by influenza and parainfluenza viruses and the impact of these changes on immunity in general.A large number of studies have documented that increasing age is associated with a progressive decline in the capacity to mount effective immune responses (Burns et al., 1993;Cook et al., 1987;Effros, 2003;Grubeck-Loebenstein and Wick, 2002;Linton and Dorshkind, 2004;McElhaney, 2003;McElhaney, 2005;Miller, 1991;Miller, 1996;Murasko and Jiang, 2005;Nagelkerken et al., 1991;Phair et al., 1978;Wick et al., 2000;Zheng et al., 1997). Aged individuals typically have an impaired capacity to clear infections and also exhibit significant defects in graft rejection, delayed type hypersensitivity, and tumor rejection (Haynes and Eaton, 2005;Miller, 1996;Po et al., 2002). These defects have important clinical consequences for the elderly in terms of susceptibility to infection and poor vaccine efficacy. Recent studies have implicated both the cellular and humoral arms of the immune response in this age-related decline in immune function. For example, studies in animals and humans have shown that aged individuals have a significantly reduced capacity to mount an effective antibody response following infection or vaccination, which is thought to be a consequence of dysfunctional aged CD4 + T cell "help" (High, 2004;Johnson and Cambier, 2004). In addition, involution of the thymus results in a decline in naïve T cell numbers, potentially limiting the breadth and quality of the repertoire of the T cell response (Naylor et al., 2005). However, we still lack a solid understanding of the scope of immune defects or mechanisms underlying the decline in immune efficacy in the elderly.Whereas most studies addressing the impact of aging on immunity have focused on immune responses to newly encountered antigens, relatively little work has addressed the impact of age on pre-existing memory T cell populations. Studies by Kapasi et al using a systemic viral model in mice demonstrated that CD8 + T cell memory remains functional for over a year after its initial generation (Kapasi et al., 2002). This is consistent with human studies suggesting that cellular immunity is relatively long lived (Hammarlund et al., 2003). However, the relative efficacy of the recall of long-term T cell memory (ie. memory that was originally established

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Section: (I) Basic Features Of the Cd8 + T Cell Recall Response To Rementioning

confidence: 99%

Aging and CD8+ T cell immunity to respiratory virus infections

Ely

Roberts

Kohlmeier

et al. 2007

Experimental Gerontology

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“…More recently, it has been suggested that a better correlate of protective cellular immunity may be the population of virus-specific T cells that become established in the lungs of mice after virus infection [2]. These cells have been found to persist in both the airways and lung parenchyma after infection with influenza, Sendai and respiratory syncytial viruses [2][3][4]; they do not cycle, have a half life of about 40 days, but upon re-exposure to antigen can proliferate and express a highly activated phenotype and cytolytic function. It has been proposed that these cells secrete cytokines and other mediators in the lung upon reexposure to virus, which recruit additional T cells from the conventional memory pool in the lymph nodes and spleen back into the lungs to control the infection.…”

Section: Induction Of Cd8mentioning

confidence: 99%

Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza

et al. 2006

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The longevity of the influenza virus-specific CD8 + T cell response following intranasal delivery of a synthetic lipopeptide was investigated and the characteristics and location of the cells associated with viral clearance examined. The lipopeptide, incorporating an epitope for CD8 + T cells and another for CD4 + T cells with the lipid moiety S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam2Cys) attached, induced potent and long-lived pulmonary protection. Both the lipopeptide and its largely unprotective non-lipidated counterpart elicited comparable numbers of CD8 + T cells in the spleen, which was the main location of the memory pool. However, the lipopeptide, unlike the non-lipidated peptide, also induced a substantial memory population that remained in the lungs and was rapidly activated upon viral challenge months later. These lipopeptide-induced lung-resident CD8 + T cells were also very similar in number and IFN-c-secreting potential to those induced by prior exposure to the virus itself and are likely mediators of initial viral clearance prior to recruitment from the expanding lymph node T cell pool. Significant clearing responses were demonstrated as late as 9 months post-lipopeptide vaccination. This study shows that CD8 + T cells primed by the lipopeptide are not only long-lived but can take up residence in the lung where they are important early mediators of pulmonary protection.

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“…Similar to memory CD8 ϩ T cells in secondary lymphoid organs, memory cells in the lung airways are small resting cells (9). However, they are phenotypically distinct from memory T cells in secondary lymphoid organs in that they express acute activation markers and have reduced CD11a expression (4,7,10). Based on their activated phenotype, memory T cells in peripheral sites are frequently referred to as effector/ memory T cells (11).…”

mentioning

confidence: 99%

Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections

Ely

Cauley

Roberts

et al. 2003

The Journal of Immunology

129

144

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Previous studies have shown that heterologous viral infections have a significant impact on pre-existing memory T cell populations in secondary lymphoid organs through a combination of cross-reactive and bystander effects. However, the impact of heterologous viral infections on effector/memory T cells in peripheral sites is not well understood. In this study, we have analyzed the impact of a heterologous influenza virus infection on Sendai virus-specific CD8+ effector/memory cells present in the lung airways. The data show a transient increase in the numbers of Sendai virus nucleoprotein 324–332/Kb-specific CD8+ memory T cells in the airways of the influenza-infected mice peaking around day 4 postinfection. Intratracheal transfer studies and 5-bromo-2′-deoxyuridine incorporation demonstrate that this increase is due to the recruitment of resting memory cells into the airways. In addition, the data show that these immigrating memory cells are phenotypically distinct from the resident memory T cells of the lung airways. A similar influx of nonproliferating Sendai virus nucleoprotein 324–332/Kb-specific CD8+ memory T cells is also induced by a secondary (homologous) infection with Sendai virus. Together, these data suggest that inflammation can accelerate memory T cell migration to nonlymphoid tissues and is a part of the normal recall response during respiratory infections.

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Long-term persistence and reactivation of T cell memory in the lung of mice infected with respiratory syncytial virus

Cited by 86 publications

References 23 publications

Aging and CD8+ T cell immunity to respiratory virus infections

Aging and CD8+ T cell immunity to respiratory virus infections

Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza

Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections

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Long-term persistence and reactivation of T cell memory in the lung of mice infected with respiratory syncytial virus

Cited by 86 publications

References 23 publications

Aging and CD8+ T cell immunity to respiratory virus infections

Aging and CD8+ T cell immunity to respiratory virus infections

Intranasal lipopeptide primes lung‐resident memory CD8+ T cells for long‐term pulmonary protection against influenza

Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections

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Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza