Interleukin-21-Producing HIV-1-Specific CD8 T Cells Are Preferentially Seen in Elite Controllers

Williams, LaTonya D.; Bansal, Anju; Sabbaj, Steffanie; Heath, Sonya L.; Song, Wei; Tang, Jianming; Zajac, Allan

doi:10.1128/jvi.01476-10

Cited by 84 publications

(75 citation statements)

References 43 publications

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“…Moreover, the data also indicate that IL-13-and IL-21-secreting HIV-specific T cells before ATI are associated with a lower viral replication following ATI, an immunological feature described in elite controllers [14,15]. As observed following therapeutic immunization of patients or in models of SIV pathogenesis, the ability to produce IL-2 CD4 + T cells appears to be critical for the maintenance of the proliferative capacity of CD8 + T cells [16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

et al. 2014

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Eur. J. Immunol. 2014Immunol. . 44: 2802Immunol. -2810 Clinical immunology 2803 IntroductionTo date, no effective therapeutic or prophylactic HIV vaccines are yet available. Recent encouraging results from the RV 144 trial showed a modest but statistically significant 31% reduction in the rate of HIV infection in vaccinated healthy volunteers receiving a prophylactic vaccine [1]. However, immune responses that would eradicate or control HIV are likely to be different from those needed to prevent primary infection. Indeed, eradication of HIV infection is likely to depend on the establishment of strong cytotoxic T lymphocytes, while prevention of infection will likely depend on the establishment of antibodies neutralizing the virus [2,3]. In both cases, CD4 + T helper cells are necessary for the establishment of robust and long-lasting immunity. Several candidate vaccines are under evaluation including peptides, inactivated virus, viral vectors, and ex vivo-generated DCs [4]. The latter represents an approach to optimize the induction of immune responses [5]. To date, only two studies, in which DCs have been loaded with chemically inactivated autologous virus, have reported a decrease in viral load [6,7]. Another approach using DCs transfected with RNA isolated from autologous virus yielded immune responses without control of viral replication [8]. However, these very promising data with inactivated autologous virus still need to be reproduced. For large scale use of DC vaccination, it would be advantageous to identify an antigenic cargo that could be used without having to isolate and expand the autologous virus which necessitates antiretroviral treatment interruption. We report here the safety and immunogenicity of a new DC platform loaded with five HIV-1-derived lipopeptides (LP) [9] in HIV-1-infected patients treated with highly active antiretroviral treatment (HAART). The study design included a 6-month analytical treatment interruption (ATI), a period which allowed us to evaluate the effects of vaccine-elicited immune responses on viral replication (Fig. 1). Results Patients and study outcomesTwenty patients were screened and 19 were enrolled within 17 months. Baseline characteristics of patients are reported in Table 1. All patients received the four vaccinations with no changes in vaccine dose. All patients but one completed the trial at 48 weeks.The vaccination was well tolerated. Two patients reached a safety endpoint (CD4 + T-cell counts below 500 cells/μL) during the vaccination phase while no safety endpoints were observed during the ATI phase. Systemic or local adverse events were mild or moderate (grade 1 or 2) and resolved in less than 2 days in the majority of cases. All patients stopped HAART at 24 weeks post inclusion except two of them who stopped at 25 and 26 weeks.Through 48 weeks, eight patients reached the immunology endpoint defining a failure of the strategy: at 28 (two patients), 32 (three patients), 36, 40, and 44 weeks. Three of these patients resumed HAART. No clinical events or pro...

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Section: Discussionmentioning

confidence: 99%

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

et al. 2014

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“…Both CD4 + and CD8 + T cells were able to produce IL-21 in response to HIV-1 infection [88]. A longitudinal and cross-sectional study showed that the frequencies of IL-21-producing HIV-specific, Ag-experienced CD4 + T cells were decreased in HIV-infected viremic patients.…”

Section: Il-21 In Hivmentioning

confidence: 99%

“…IL-21-producing CD4 + T cells likely contribute to viral containment by promoting CD8 + T cell activation and maintenance [90][91][92][93]. Meanwhile, HIV-1-specific IL-21-producing CD8 + T cells were also induced following primary infection and play a critical role in the maintenance of viremia control [88]. PBMCs from healthy donors were infected with HIV-1 in vitro, suppression of granulysin expression by CD8 These findings indicate that the IL-21 concentrations may serve as a useful biomarker for monitoring HIV disease progression and the cytokine may be of great importance for vaccine design [99].…”

Section: Il-21 In Hivmentioning

confidence: 99%

IL-21 and Related Diseases

Niu¹,

Chen²

2011

J Clin Cell Immunol

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IL-21, which is produced by activated NKT cells and CD4 + T cells, exhibits pleiotropic effects not only on a variety of immune cells but also on non-immune cells. It has been demonstrated that IL-21 plays significant roles in the process of autoimmune diseases, inflammatory diseases and cancers. This review intends to give the reader an overview of this cytokine and the relationships between IL-21 and the related diseases of different body systems.

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“…L'IL-21 produite par ces cellules augmente la production de perforine par les cellules T CD8 + spécifiques du VIH-1 provenant de patients chroniquement infectés dont la maladie progresse et augmente l'effet inhibiteur de ces cellules sur la réplication du VIH-1 [24]. Une étude a de plus récemment démontré que les cellules T CD8 + des patients « contrôleurs élites » sont aussi capables de produire de l'IL-21 lors d'une stimulation peptidique spécifique du VIH-1 [26]. Il est important de noter ici que ces cellules ne produisent pas d'IL-21 habituellement.…”

Section: Revuesunclassified

L’interleukine-21, une cytokine clé dans le contrôle du VIH et d’autres infections virales chroniques

Iannello¹,

Allam²,

Samarani³

et al. 2012

Med Sci (Paris)

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Interleukin-21-Producing HIV-1-Specific CD8 T Cells Are Preferentially Seen in Elite Controllers

Cited by 84 publications

References 43 publications

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

IL-21 and Related Diseases

L’interleukine-21, une cytokine clé dans le contrôle du VIH et d’autres infections virales chroniques

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