Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure

Harari, Alexandre; Enders, Felicitas Bellutti; Cellerai, Cristina; Bart, Pierre‐Alexandre; Pantaleo, Giuseppe

doi:10.1128/jvi.02528-08

Cited by 107 publications

(108 citation statements)

References 66 publications

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“…First, the readouts -once IFN-g secretion and once CTL responses -were different. Second, while we assessed ex vivo responses in our previous report, we used here effector cells stimulated in vitro for 11 to 14 days in the presence of exogenous IL-2, a condition that has been shown to modify CTL activity [32]. Finally and most importantly, here, we examined whether an intrathecal EBV-specific CD8 1 T-cell response was present in the different categories of patients.…”

Section: Discussionmentioning

confidence: 99%

Intrathecal immune responses to EBV in early MS

et al. 2010

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EBV has been consistently associated with MS, but its signature in the CNS has rarely been examined. In this study, we assessed EBV-specific humoral and cellular immune responses in the cerebrospinal fluid (CSF) of patients with early MS, other inflammatory neurological diseases (OIND) and non-inflammatory neurological diseases (NIND). The neurotropic herpesvirus CMV served as a control. Virus-specific humoral immune responses were assessed in 123 consecutive patients and the intrathecal recruitment of virus-specific antibodies was expressed as antibody indexes. Cellular immune responses tested in the blood of 55/123 patients were positive in 46/55. The CD8 1 CTL responses of these 46 patients were assessed in the blood and CSF using a CFSE-based CTL assay. We found that viral capsid antigen and EBV-encoded nuclear antigen-1, but not CMV IgG antibody indexes, were increased in early MS as compared with OIND and NIND patients. There was also intrathecal enrichment in EBV-, but not CMV-specific, CD8 1 CTL in early MS patients. By contrast, OIND and NIND patients did not recruit EBV-nor CMV-specific CD8 1 CTL in the CSF. Our data, showing a high EBV-, but not CMV-specific intrathecal immune response, strengthen the association between EBV and MS, in particular at the onset of the disease.

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Section: Discussionmentioning

confidence: 99%

Intrathecal immune responses to EBV in early MS

et al. 2010

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“…T lymphocytes only play a secondary role in this damage. Moreover, CD8 + T lymphocytes have a poor cytotoxic profile after influenza virus infection (18), and lymphopenia can be observed (1). We hypothesize that the influenza virus itself plays an active role in these findings.…”

Section: Nfluenza a Virus Infection Causes Severe Disease In Humansmentioning

confidence: 81%

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

Vogel

Haasbach

Reiling

et al. 2010

The Journal of Immunology

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Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in humans. Still, the basis for their increased pathogenesis remains unclear. Additionally, the high morbidity in the younger population stays inexplicable, and the recent pandemic H1N1v outbreak in 2009 demonstrated the urgent need for a better understanding about influenza virus infection. In the present study, we demonstrated that HPAIV infection of mice not only led to lung destruction but also to functional damage of the thymus. Moreover, respiratory dendritic cells in the lung functioned as targets for HPAIV infection being able to transport infectious virus from the lung into the thymus. The pandemic H1N1 influenza virus was able to infect respiratory dendritic cells without a proper transport to the thymus. The strong interference of HPAIV with the immune system is especially devastating for the host and can lead to lymphopenia. In summary, from our data, we conclude that highly pathogenic influenza viruses are able to reach the thymus via dendritic cells and to interfere with T lymphocyte development. Moreover, this exceptional mechanism might not only be found in influenza virus infection, but also might be the reason for the increased immune evasion of some new emerging pathogens.

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“…4C). Of note, we recently showed that perforin was the best predictor of the cytotoxic capacity of virus-specific CD8 + T cells [29]. We thus assessed perforin expression and did not observe increased perforin expression in HIV-specific CD8 + T-cell responses following NYVAC-B immunization (data not shown).…”

Section: Hiv-specific Cd8 + T-cell Responses Against Optimal Epitopesmentioning

confidence: 99%

NYVAC immunization induces polyfunctional HIV‐specific T‐cell responses in chronically‐infected, ART‐treated HIV patients

et al. 2012

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We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intramuscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4 + and CD8 + T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field. Eur. J. Immunol. 2012. 42: 3038-3048 Clinical immunology 3039 IntroductionThe development of antiviral therapy has dramatically changed the course and the prognosis of HIV infection. More than 30 antiviral drugs available offer many therapeutic options for the patients and some of these drugs used in combination are able to induce long-term suppression of virus replication as indicated by the persistence of levels of viremia below the limit of detection of highly sensitive PCR assays [1]. The antiviral therapy-mediated suppression of virus replication has resulted in dramatic reduction of morbidity and mortality, and HIV infection has shifted from being a life threatening to a chronic viral disease [2]. In this regard, recent studies have estimated a life expectancy of 25-30 years for subjects with HIV infection [3,4]. Despite the long-term suppression of virus replication and the normalization of a series of immunological parameters, which are not limited to the CD4 + T-cell counts but also to the recovery of a series of antigen-specific (including HIV) immunological functions, the interruption of antiviral therapy is almost invariably associated to virus rebound [1,5]. These observations indicated that the long-term suppression of virus replication does not result in the generation of an effective HIV-specific immune response [6].For these reasons, a number of immunological interventions have been investigated in the past and are currently being investigated to stimulate HIV-specific immune responses that may efficiently control HIV replication also in the absence of antiviral therapy. Among these interventions, particular attention has been given to the development of therapeutic v...

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Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure

Cited by 107 publications

References 66 publications

Intrathecal immune responses to EBV in early MS

Intrathecal immune responses to EBV in early MS

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

NYVAC immunization induces polyfunctional HIV‐specific T‐cell responses in chronically‐infected, ART‐treated HIV patients

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