New advances in CMV and immunosenescence

Sansoni, Paolo; Vescovini, Rosanna; Fagnoni, Francesco; Akbar, Arne N.; Arens, Ramon; Chiu, Yen‐Ling; Čičin‐Šain, Luka; Déchanet‐Merville, Julie; Derhovanessian, Evelyna; Ferrando‐Martínez, Sara; Franceschi, Claudio; Frasca, Daniela; Fülöp, Tamás; Furman, David; Gkrania‐Klotsas, Effrossyni; Goodrum, Felicia; Grubeck‐Loebenstein, Beatrix; Hurme, Mikko; Kern, Florian; Lilleri, Daniele; López‐Botet, Miguel; Maier, Andrea B.; Marandu, Thomas F.; Marchant, Arnaud; Matheï, Catharina; Moss, Paul; Muntasell, Aura; Remmerswaal, Ester B. M.; Riddell, Natalie E.; Rothe, Kathrin; Sauce, Delphine; Shin, Eui‐Cheol; Simanek, Amanda M.; Smithey, Megan J.; Söderberg‐Nauclér, Cecilia; Solana, Rafael; Thomas, Paul G.; Lier, R. A. W. Van; Pawelec, Graham; Nikolich‐Žugich, Janko

doi:10.1016/j.exger.2014.03.020

Cited by 126 publications

(97 citation statements)

References 29 publications

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“…Unfortunately, we have no information on CMV infection status of the individuals in our study, which is known to influence immunosenescence (87). We could expect that the cohort of oldest individuals who overcame the age-selection barrier is enriched with CMVnegative individuals, for which the percentage of naive CD4 + T cells was shown to be more stable with aging (88).…”

Section: Discussionmentioning

confidence: 92%

Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians

Britanova

Shugay

Merzlyak

et al. 2016

The Journal of Immunology

147

180

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The diversity, architecture, and dynamics of the TCR repertoire largely determine our ability to effectively withstand infections and malignancies with minimal mistargeting of immune responses. In this study, we have employed deep TCRβ repertoire sequencing with normalization based on unique molecular identifiers to explore the long-term dynamics of T cell immunity. We demonstrate remarkable stability of repertoire, where approximately half of all T cells in peripheral blood are represented by clones that persist and generally preserve their frequencies for 3 y. We further characterize the extremes of lifelong TCR repertoire evolution, analyzing samples ranging from umbilical cord blood to centenarian peripheral blood. We show that the fetal TCR repertoire, albeit structurally maintained within regulated borders due to the lower numbers of randomly added nucleotides, is not limited with respect to observed functional diversity. We reveal decreased efficiency of nonsense-mediated mRNA decay in umbilical cord blood, which may reflect specific regulatory mechanisms in development. Furthermore, we demonstrate that human TCR repertoires are functionally more similar at birth but diverge during life, and we track the lifelong behavior of CMV- and EBV-specific T cell clonotypes. Finally, we reveal gender differences in dynamics of TCR diversity constriction, which come to naught in the oldest age. Based on our data, we propose a more general explanation for the previous observations on the relationships between longevity and immunity.

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Section: Discussionmentioning

confidence: 92%

Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians

Britanova

Shugay

Merzlyak

et al. 2016

The Journal of Immunology

147

180

View full text Add to dashboard Cite

show abstract

“…Both forms of infection are targets of the host immune response. It should be noted that CMV latency remains poorly defined in terms of quantitative measures of host cell and viral gene expression to differentiate latency from reactivation, and for interactions of latent CMV with the immune system (86,87). Latently infected cells include ECs and CD34+ hematopoietic progenitor cells and monocytes/macrophages in both humans and animals (88).…”

Section: Viral Genetics and Variability In Immune Responsementioning

confidence: 99%

The Cell Biology of Cytomegalovirus: Implications for Transplantation

Kaminski

Fishman

2016

American Journal of Transplantation

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Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and cd T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation.

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“…CMV is often considered to be an immunological burden within the T cell compartment that exerts mainly negative effects on immune status and overall health [27]; however, it has been suggested recently that latent herpesviruses may play a pivotal role in 'arming' NK cells to destroy target cells adequately [28]. Mice with latent murid herpesvirus 4 infection show increased granzyme B protein expression, interferon (IFN)-g production and NK cell cytotoxicity, which can protect against a lethal lymphoma challenge [28].…”

Section: Introductionmentioning

confidence: 99%

Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

Bigley

Rezvani

Shah

et al. 2016

Clinical and Experimental Immunology

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SummaryCytomegalovirus (CMV) infection markedly expands NKG2C1/NKG2A2 NK cells, which are potent killers of infected cells expressing human leucocyte antigen (HLA)-E. As HLA-E is also over-expressed in several haematological malignancies and CMV has been linked to a reduced risk of leukaemic relapse, we determined the impact of latent CMV infection on NK cell cytotoxicity against four tumour target cell lines with varying levels of HLA-E expression. NK cell cytotoxicity against K562 (leukaemia origin) and U266 (multiple myeloma origin) target cells was strikingly greater in healthy CMV-seropositive donors than seronegative donors and was associated strongly with target cell HLA-E and NK cell NKG2C expression. NK cell cytotoxicity against HLA-E transfected lymphoma target cells (221.AEH) was $threefold higher with CMV, while NK cell cytotoxicity against non-transfected 721.221 cells was identical between the CMV groups. NK cell degranulation (CD107a

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New advances in CMV and immunosenescence

Cited by 126 publications

References 29 publications

Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians

Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians

The Cell Biology of Cytomegalovirus: Implications for Transplantation

Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

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