Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus

Larsson, Marie; Fonteneau, Jean-François; Lirvall, Margareta; Haslett, Patrick; Lifson, Jeffrey D.; Bhardwaj, Nina

doi:10.1097/00002030-200207050-00003

Cited by 106 publications

(83 citation statements)

References 40 publications

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“…Chemical inactivation with AT-2, which preserves the native morphology of viral particles (53), provided encouraging immune results in eliciting HLA-I responses (22,54,55), but its use in human clinical trials is not approved by European regulatory authorities. Thus, novel delivery tools for cell therapy vaccination and new methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate with Better T Cell Activation

Rodriguez-Plata

Urrutia

Cardinaud

et al. 2012

The Journal of Immunology

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During HIV-1 infection, dendritic cells (DC) facilitate dissemination of HIV-1 while trying to trigger adaptive antiviral immune responses. We examined whether increased HIV-1 capture in DC matured with LPS results in more efficient Ag presentation to HIV-1–specific CD4+ and CD8+ T cells. To block the DC-mediated trans-infection of HIV-1 and maximize Ag loading, we also evaluated a noninfectious integrase-deficient HIV-1 isolate, HIVNL4-3ΔIN. We showed that higher viral capture of DC did not guarantee better Ag presentation or T cell activation. Greater HIVNL4-3 uptake by fully LPS-matured DC resulted in higher viral transmission to target cells but poorer stimulation of HIV-1–specific CD4+ and CD8+ T cells. Conversely, maturation of DC with LPS during, but not before, viral loading enhanced both HLA-I and HLA-II HIV-1–derived Ag presentation. In contrast, DC maturation with the clinical-grade mixture consisting of IL-1β, TNF-α, IL-6, and PGE2 during viral uptake only stimulated HIV-1–specific CD8+ T cells. Hence, DC maturation state, activation stimulus, and time lag between DC maturation and Ag loading impact HIV-1 capture and virus Ag presentation. Our results demonstrate a dissociation between the capacity to capture HIV-1 and to present viral Ags. Integrase-deficient HIVNL4-3ΔIN was also efficiently captured and presented by DC through the HLA-I and HLA-II pathways but in the absence of viral dissemination. HIVNL4-3ΔIN seems to be an attractive candidate to be explored. These results provide new insights into DC biology and have implications in the optimization of DC-based immunotherapy against HIV-1 infection.

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Section: Discussionmentioning

confidence: 99%

HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate with Better T Cell Activation

Rodriguez-Plata

Urrutia

Cardinaud

et al. 2012

The Journal of Immunology

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“…Other viral antigens have also been shown to be cross-presented in vitro including vaccinia virus, canarypox virus, HIV and HCMV, amongst others [78][79][80][81][82][83]. This crosspresentation suggests a mechanism for the antigen transfer between DC subtypes observed in murine models and suggests that the immunoevasive mechanisms of costimulatory molecule downregulation and apoptosis of DC by HSV can be counteracted by uptake by bystander DC.…”

Section: Subsets In Innate and Adaptive Immunity To Hsvmentioning

confidence: 95%

Langerhans cells and viral immunity

2008

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Langerhans cells (LC) are a unique dendritic cell subset that are located in mucosal stratified squamous epithelium and skin epidermis. Their location is ideally suited for their function as antigen presenting cells that capture invading viruses and induce anti-viral immunity. However, it is becoming evident that the interaction between LC and viruses can result in different responses, depending on the virus and the receptors involved. Here we will discuss the recent data on the similarities and differences in roles of LC in viral immunity to and infection with HIV, herpes simplex and varicella-zoster virus. Although all three viruses interact with LC during initial infection, the effects can be quite different, reflecting differences in biology and pathogenesis. Key words: Dendritic cells Á Langerhans cells Á Infectious diseases Á HIV Á HerpesvirusesSee accompanying mini-review by Kaplan et al. Biology of LC and interactions with virusesThe resident epidermal dendritic cells (DC), Langerhans cells (LC), form a tight network with each other and with the surrounding keratinocytes via E-cadherin in the skin or mucosal stratified squamous epithelium. In the anogenital region they are distributed throughout the anogenital skin and mucosa including vagina, ectocervix as well as male foreskin. In stratified squamous epithelium, LC overlie interstitial or dermal DC [1]. LC can repopulate from local and blood-borne precursors (reviewed by Kaplan et al. in this issue [2]). Similar to other myeloid DC, LC are able to bridge innate and adaptive immunity. They are able to interact directly with microorganisms at the periphery to produce effector cytokines and initiate or restimulate activation of T and B lymphocytes through antigen presentation. LC express different pattern recognition receptors such as C-type lectin receptors (CLR) and Toll-like receptors (TLR), to bind and capture pathogens. These interactions result in activation of intracellular signalling pathways leading to LC activation and cytokine induction. The CLR expressed by skin DC differ by site: Langerin by epidermal LC and DC-SIGN and mannose receptor by dermal DC. LC like other migratory DC are in an immature, highly endocytic state while sessile in the skin/mucosa. However after pathogen binding to TLR and uptake, LC become mature and migratory, downregulating their endocytic and antigen processing capacity. Mature LC migrate to the lymph nodes where they are directly or indirectly involved in presentation of pathogenderived antigens on MHC Class I and II to T cells, resulting in activation of antigen-specific T cells [2][3][4]. Recent studies have raised the possibility that LC may have an immunosuppressive role [5][6][7]. Kaplan et al. [2] showed that contact hypersensitivity was amplified on LC ablation, while Cumberbatch et al.[5] found defective LC mobilisation in patients with psoriasis. Immunosuppression rather than stimulation could be explained, in part, by the maturational process associated with LC migration during steady-state conditions. Jian...

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“…HLA-A2), Gag 20 -28 (RLRPGGKKK, HLA-A3), and human T-lymphotrophic virus-1 Tax [11][12][13][14][15][16][17][18][19] (LLFGYPVYV, HLA-A2) were from Neosystem (Strasbourg, France). The following mAbs were used: anti-MHC class I W6͞32 ascitis (1:100), anti-CD11c (pure or phycoerythrin-labeled) and anti-CD3-FITC (Becton Dickinson), and GaMIg-Cy5 (Caltag, South San Francisco, CA).…”

Section: Methodsmentioning

confidence: 99%

“…DC have developed specific cross-presentation pathways that allow MHC class I-restricted presentation of the antigens contained in these apoptotic cells to CD8 ϩ T lymphocytes (9,10). DC from HIV ϩ patients can activate autologous CD4 ϩ and CD8 ϩ lymphocytes after coculture with infected apoptotic cells (11,12). An alternative source of HIV antigens for DC may be defective viral particles, which can fuse with the plasma membrane and be cross-presented without viral replication (13).…”

mentioning

confidence: 99%

Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4 ⁺ T lymphocytes

Marañón

Desoutter

Hoeffel

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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A better understanding of the antigen presentation pathways that lead to CD8 ؉ T cell recognition of HIV epitopes in vivo is needed to achieve better immune control of HIV replication. Here, we show that cross-presentation of very small amounts of HIV proteins from apoptotic infected CD4 ؉ T lymphocytes by dendritic cells to CD8 ؉ T cells is much more efficient than other known HIV presentation pathways, i.e., direct presentation of infectious virus or crosspresentation of defective virus. Unexpectedly, dendritic cells also take up actively antigens into endosomes from live infected CD4 ؉ T lymphocytes and cross-present them as efficiently as antigens derived from apoptotic infected cells. Moreover, live infected CD4 ؉ T cells costimulate cross-presenting dendritic cells in the process. Therefore, dendritic cells can present very small amounts of viral proteins from infected T cells either after apoptosis, which is frequent during HIV infection, or not. Thus, if HIV expression is transiently induced while costimulation is enhanced (for instance after IL-2 and IFN␣ immune therapy), this HIV antigen presentation pathway could be exploited to eradicate latently infected reservoirs, which are poorly recognized by patients' immune systems.

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Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus

Abstract: These sources of antigens may be critical for the generation and maintenance of anti-HIV-1 immunity by DC.

Cited by 106 publications

References 40 publications

HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate with Better T Cell Activation

HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate with Better T Cell Activation

Langerhans cells and viral immunity

Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4 ⁺ T lymphocytes

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Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus

Abstract: These sources of antigens may be critical for the generation and maintenance of anti-HIV-1 immunity by DC.

Cited by 106 publications

References 40 publications

HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate with Better T Cell Activation

HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate with Better T Cell Activation

Langerhans cells and viral immunity

Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4 + T lymphocytes

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Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4 ⁺ T lymphocytes