Distinct Natural Killer Cells in HIV-Exposed Seronegative Subjects With Effector Cytotoxic CD56dim and CD56bright Cells and Memory-Like CD57+NKG2C+CD56dim Cells

Lima, Jozely Francisca Mello; Oliveira, Luanda Mara da Silva; Pereira, Newton Lindolfo; Mitsunari, Gabrielle Eimi; Duarte, Alberto J. S.; Sato, Maria Notomi

doi:10.1097/qai.0000000000000350

Cited by 24 publications

(22 citation statements)

References 40 publications

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“…The robust, non-specific SEB-induced polyfunctional response of circulating CD4+ and CD8+ T cells in EU subjects, despite HIV-1 exposure, could also occur in response to exposure to other viruses, such as cytomegalovirus (CMV). In fact, previously we verified 100% frequency of CMV seropositivity in EU individuals, similarly to HIV, whereas only 65% seropositivity is found in healthy control individuals 26 . Indeed, CMV seropositive donors have higher numbers of polyfunctional CD8+ T cells associated with the expansion of polyfunctional CD8+ CD57+ T cells, indicating that CMV improves the CD8 response to SEB 27 .…”

Section: Discussionmentioning

confidence: 68%

Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38− T cells in HIV-exposed uninfected subjects

Oliveira

Lima

Cervantes

et al. 2015

Sci Rep

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Some individuals are resistant to HIV-1 infection despite repeated exposure to the virus, suggesting the presence of a complex antiviral response. Innate factors like IL-22 exert gut mucosal protection and polyfunctional T cells have been associated with low progression in HIV infection; therefore, we evaluated the frequencies of CD4+ and CD8+ T cell-secreting cytokines, including Tc22/Th22 cells and polyfunctional T cells in HIV-1-exposed uninfected individuals (EUs), their HIV-1-infected partners and healthy controls. EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24. Similar responses of Th22 and Tc22 cells to Gag peptides and Staphylococcal enterotoxin B (SEB) stimulation were detected in the serodiscordant couples. However, polyfunctionality in HIV subjects was associated with an HIV Gag response of CD38+ T cells, whereas polyfunctionality for EUs was induced upon SEB stimulation by CD38- T cells. EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38- T cells with a low activation profile. These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1.

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Section: Discussionmentioning

confidence: 68%

Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38− T cells in HIV-exposed uninfected subjects

Oliveira

Lima

Cervantes

et al. 2015

Sci Rep

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“…In contrast to what is known about NK cells responding to viruses, BCG-stimulated CD56 bright cells do not seem to correspond to a population that can be defined by the expression of single or a limited number of cell surface receptors. For example, HCMV infection is associated with the expansion of a late differentiated CD57 C NKG2C C population, 27,28 that is usually CD16 low , while a CD56 dim NKG2D C NKG2A C CD57 ¡ KIR ¡ early differentiated subpopulation expands after EBV infections. 29,30 In contrast, BCG exposure clearly activates a wider range of NK cells including CD56 dim CD94 C KIR ¡ and CD56 dim CD57 C KIR C NK cells (Figs.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a human anti-tumoral NK cell population expanded after BCG treatment of leukocytes

et al. 2017

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Immunotherapy, via intra-vesical instillations of BCG, is the therapy of choice for patients with high-risk non-muscle invasive bladder cancer. The subsequent recruitment of lymphocytes and myeloid cells, as well as the release of cytokines and chemokines, is believed to induce a local immune response that eliminates these tumors, but the detailed mechanisms of action of this therapy are not well understood. Here, we have studied the phenotype and function of the responding lymphocyte populations as well as the spectrum of cytokines and chemokines produced in an model of human peripheral blood mononuclear cells (PBMCs) co-cultured with BCG. Natural killer (NK) cell activation was a prominent feature of this immune response and we have studied the expansion of this lymphocyte population in detail. We show that, after BCG stimulation, CD56 NK cells proliferate, upregulate CD56, but maintain the expression of CD16 and the ability to mediate ADCC. CD56 NK cells also contribute to this expansion by increasing CD16 and KIR expression. These unconventional CD56 cells efficiently degranulated against bladder cancer cells and the expansion of this population required the release of soluble factors by other immune cells in the context of BCG. Consistent with these data, a small, but significant increase in the intensity of CD16 expression was noted in peripheral blood CD56 cells from bladder cancer patients undergoing BCG therapy, that was not observed in patients treated with mitomycin-C instillations. These observations suggest that activation of NK cells may be an important component of the anti-tumoral immune response triggered by BCG therapy in bladder cancer.

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“…NK cells of HEU adults have been previously reported to have higher CD57 compared with those of HIV-infected patients. 34 Although the results were not significant, the frequency of CD57 alone (data not shown) and simultaneous expression of CD57, CD122, CD11b, and CD16 trended toward being higher in HEU children (Fig E7, C).…”

Section: Nk-cell Subsets Of Hiv-exposed and Hiv-infected Patients Arementioning

confidence: 77%

NK cells in treated HIV-infected children display altered phenotype and function

Mahapatra

Shearer

Minard

et al. 2019

Journal of Allergy and Clinical Immunology

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Perinatal exposure to ART/HIV HIV-infected HIV-exposed Control Greater phenotypic overlap KIR2DL1 Activating receptors Baseline CD107a NK cell NK cell NK cell NK cells from treated HIV-infected children display an activated phenotype KIR: killer cell immunoglobulin-like receptor Activating receptor: +++ KIR2DL1: + Baseline CD107a: +++++ Activating receptor: ++ KIR2DL1: ++ Baseline CD107a: +++ Activating receptor: + Baseline CD107a: +++ Background: Chronic HIV infection is known to trigger a population redistribution and alteration in the functional capacity of natural killer (NK) cells. Because of improved antiretroviral treatments, there are rising numbers of adolescents and young adults worldwide who are living with HIV infection since birth. Objective: We sought to determine how NK-cell phenotypic and functional subsets are altered in treated pediatric patients. Methods: NK cells were contrasted among 29 HIV-unexposed and uninfected controls (5-19 years), 23 HIV-exposed but uninfected patients (3-19 years), and 25 HIV-infected patients (3-19 years) using multiparametric flow cytometry. Results: Although most NK-cell markers did not differ, activating receptors such as NKp46, DNAX accessory molecule-1, and NKG2C and stimulatory receptors such as CD2 and CD11c were expressed by a higher frequency of NK cells in HIV-infected patients than in controls. Interestingly, there were less differences between HIV-infected and HIV-exposed but uninfected children. There was an inverse relationship between CD4/CD8 T-cell ratio (as a marker of disease progression) and CD11c and NKG2C frequency and CD69 upregulation on stimulation among HIV-infected patients. Conclusions: A chronic NK-cell activation phenotype persists in HIV-infected children receiving antiretroviral therapy and is associated with declining CD4/CD8 T-cell ratios. A lower CD4/ CD8 T-cell ratio was associated with higher baseline granzyme B (P 5 .0068; R 2 5 0.29) and degranulation potential (P 5 .022; R 2 5 0.22) in stimulated NK cells. Thus, NK cells in HIVinfected children receiving treatment have reduced functional potential and an activated phenotype that distinguishes them

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Distinct Natural Killer Cells in HIV-Exposed Seronegative Subjects With Effector Cytotoxic CD56dim and CD56bright Cells and Memory-Like CD57+NKG2C+CD56dim Cells

Cited by 24 publications

References 40 publications

Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38− T cells in HIV-exposed uninfected subjects

Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38− T cells in HIV-exposed uninfected subjects

Characterization of a human anti-tumoral NK cell population expanded after BCG treatment of leukocytes

NK cells in treated HIV-infected children display altered phenotype and function

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