CD27 is required for generation and long-term maintenance of T cell immunity

Hendriks, Jenny; Gravestein, Loes A.; Tesselaar, Kiki; Lier, R. A. van; Schumacher, Ton N.; Borst, Jannie

doi:10.1038/80877

Cited by 664 publications

(691 citation statements)

References 54 publications

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“…CD27-CD70 interactions play a decisive role in clonal expansion of primed T cells and differentiation into effector T cells. CD27-deficient mice show reduced numbers of effector and memory T cells upon influenza infection [21] whereas CD70-transgenic mice showed enhanced numbers and functionally improved effector T cells after influenza or tumor challenge [20]. In vitro studies with human CMVspecific T cells showed that the antigen dose positively correlated with the CD70 expression levels that are induced [27].…”

Section: Discussionmentioning

confidence: 99%

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Properties of murine CD8+CD27- T cells

et al. 2005

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Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that the interaction between CD27 and its cellular ligand CD70 regulates formation of effector and memory T cells after antigenic challenge in vivo [20][21][22]. In humans, CD27 is expressed on all naive T cells and is markedly up-regulated early after activation [23,24].…”

Section: Introductionmentioning

confidence: 99%

Properties of murine CD8+CD27- T cells

et al. 2005

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“…Among the subsets of CD8 + T cells, CD8 + CD45RO À CD27 À cells are considered to be responsible for effector functions (Hamann et al, 1997;Sallusto et al, 1999;Baares et al, 2000). The phenotypic and functional characteristics of these cells have been extensively investigated and are consistent with their status of antigen-primed effector cells (Baares et al, 2000;Hendrics et al, 2000). In tumour-bearing hosts, these cells are likely to play an important role in the control of tumour growth.…”

Section: Discussionmentioning

confidence: 99%

Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

et al. 2003

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A subset of circulating T cells (CD8 + CD45RO À CD27 À ) with a naïve phenotype, but mediating effector function, is considered to play an important role in host antitumour defence. To investigate the attributes of these effector T cells in patients with squamous cell carcinoma (SCC) of the head and neck cancer, venous blood was obtained from 39 individuals with cancer and 45 normal controls (NC). Peripheral blood mononuclear cells were isolated, stained with labelled monoclonal antibodies specific for CD8, CD45RO, CD45RA, CD62L, CD27, TCR-z as well as isotype controls and examined by multicolour flow cytometry. Annexin V binding to CD8 + T cells and PMA/ionomycin-induced IFN-g expression were also evaluated in patients and NC. The proportions of CD45RA + CD45RO À (naïve) and CD45RA À CD45RO + (memory) cells were found to be comparable within the CD8 + T-cell subset. However, relative to NC, the frequency of effector CD8 + CD45RO À CD27 À cells was strikingly increased in all SCC patients regardless of the disease status (P ¼ 0.0003). The proportion of these cells was found to increase with age in both patients and NC. In NC, stimulated IFN-g expression was largely restricted to CD8 + CD45RO À CD27 + cells, while in patients CD8 + CD45RO À CD27 À expressed IFN-g after ex vivo stimulation. Expression of the TCR-associated z chain was decreased or absent in freshly isolated CD8 + CD45RO À CD27 À T cells in patients (Po0.0001). Annexin V was found to bind to a higher proportion of circulating CD8 + T cells in patients than NC (Po0.006), and significantly more Annexin V + T cells were present in the effector (Po0.0059) than the naïve subset within the CD8 + CD45RO À compartment. The data indicate that the expanded CD8 + CD45RO À CD27 À T cells, which contain precursors of IFN-g-producing T cells, are z-negative and sensitive to apoptosis in the circulation of patients with HNC.

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“…Furthermore, CD27 signalling promotes T helper type 1 responses9, 10 and is important, albeit not essential, for memory differentiation of CD8 T cells 11, 12, 13. The requirement for CD27/CD70 co‐stimulation seems to be dependent on the viral properties.…”

Section: Introductionmentioning

confidence: 99%

“…The requirement for CD27/CD70 co‐stimulation seems to be dependent on the viral properties. CD27 signalling is required for the priming of effector cytotoxic T lymphocytes after infection of mice with influenza virus,11 vaccinia virus (VV) and vesicular stomatitis virus;14 the CD27 signal is dispensable, however, for the generation of primary lymphocytic choriomeningitis virus‐specific T‐cell responses 14, 15. The discrepancy might be partly explained by the differential capacity of the viruses to induce CD70 expression13, 14 because, apart from its constitutive expression in the thymus, CD70 expression is induced on antigen‐presenting cells (APCs) such as DCs and B cells only after activation 16, 17, 18.…”

Section: Introductionmentioning

confidence: 99%

CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

et al. 2018

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SummaryThe immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen‐presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T‐cell receptor complex a plethora of co‐stimulatory signals not only ensures a proper T‐cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The tumour necrosis factor receptor/ligand pair CD27/CD70 gained a lot of attention because of its key role in regulating T‐cell activation, survival, differentiation and maintenance, especially in the course of viral infections and cancer. We sought to investigate the role of CD70 co‐stimulation for immune responses induced by the vaccine vector modified vaccinia virus Ankara–Bavarian Nordic® (MVA‐BN ®). Short‐term blockade of CD70 diminished systemic CD8 T‐cell effector and memory responses in mice. The dependence on CD70 became even more apparent in the lungs of MHC class II‐deficient mice. Importantly, genetically encoded CD70 in MVA‐BN ® not only increased CD8 T‐cell responses in wild‐type mice but also substituted for CD4 T‐cell help. MHC class II‐deficient mice that were immunized with recombinant MVA‐CD70 were fully protected against a lethal virus infection, whereas MVA‐BN ®‐immunized mice failed to control the virus. These data are in line with CD70 playing an important role for vaccine‐induced CD8 T‐cell responses and prove the potency of integrating co‐stimulatory molecules into the MVA‐BN ® backbone.

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CD27 is required for generation and long-term maintenance of T cell immunity

Cited by 664 publications

References 54 publications

Properties of murine CD8+CD27- T cells

Properties of murine CD8+CD27- T cells

Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

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