Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2

Department of Medicine, University of California, San Francisco, San Francisco, California, United States
Blood (Impact Factor: 10.45). 05/2006; 107(8):3081-3. DOI: 10.1182/blood-2005-09-3636
Source: PubMed


Innate CD1d-restricted natural killer T (NKT) cells are infected and lost in HIV-1-infected patients, and this could contribute to HIV-1 pathogenesis because NKT cells play an important role in directing both adaptive and innate immunity. Administration of interleukin-2 (IL-2) to HIV-1-infected patients leads to substantial and sustained CD4+ T-cell expansion, involving both naive and memory cells. We investigated whether IL-2 treatment could restore the NKT cell compartment in patients with primary HIV-1 infection. We show that IL-2 combined with effective antiretroviral therapy (ART) resulted in significant expansion of CD1d-restricted NKT cells. Expansion occurred in both the CD4- and CD4+ subsets of NKT cells, and expanded cells expressed the CD161 maturation marker while expression of the HIV coreceptor CCR5 was reduced. These data indicate that IL-2 treatment in combination with effective ART is beneficial for the restoration of innate NKT cell immunity in patients with primary HIV-1 infection.

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Available from: Johan K Sandberg, Feb 17, 2014
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    • "Amongst other biological effects, IL-2 induces the proliferation of activated B-lymphocytes, boosts natural killers (NK) and cytotoxics T-lymphocyte (CTL)-mediated cytotoxicity, stimulates the production of other cytokines including TNF, IFN-γ, and GMCSF and modulates programmed cell death. [4] [5] "
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    DESCRIPTION: Preliminary Bioinformatics work
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    • "The lack of change in CD4− iNKT populations during in vitro infection suggests that loss of the CD4+ subset is not largely due to CD4 downregulation. Replication of similar studies in a number of cohorts has largely confirmed these initial observations [60]–[63], although the impact of highly active antiretroviral therapy (HAART) on iNKT cell reconstitution remains controversial [58], [64]–[66] and the kinetics of iNKT reconstitution appear to be slower than that of conventional CD4+ T cells [62], [67]. "
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    ABSTRACT: Natural killer T cells (NKT cells) represent a subset of T lymphocytes that express natural killer (NK) cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT), express a highly restricted T cell receptor (TCR) and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV) infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.
    PLoS Pathogens 08/2012; 8(8):e1002838. DOI:10.1371/journal.ppat.1002838 · 7.56 Impact Factor
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    • "This study also showed that NKT cells could be expanded in vitro in some subjects with PHA stimulation, but the resulting population was largely CD4 + and failed to secrete IFN-, making these cells a prime target for HIV-1 infection [1]. It will be important if the expansion of NKT cells could be sustained and restore their function after treatment in HIV infection [15] [33]. In HIV-2 infection, the stable population of IFN- secreting NKT cells and the relatively low frequency (compared to HIV-1) of non IFN- secreting CD4 + NKT cells in HIV-2 subsets may reduce the likelihood of this population "

    World Journal of AIDS 01/2012; 02(02):103-108. DOI:10.4236/wja.2012.22014
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