Kinetics of Myeloid-Derived Suppressor Cell Frequency and Function during Simian Immunodeficiency Virus Infection, Combination Antiretroviral Therapy, and Treatment Interruption

Dross, Sandra; Munson, Paul V.; Kim, Se Eun; Bratt, Debra; Tunggal, Hillary C.; Gervassi, Ana; Fuller, Deborah H.; Horton, Helen

doi:10.4049/jimmunol.1600759

Cited by 24 publications

(25 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In HIV-infected individuals, viral suppression by ART or HAART was shown to decrease the MDSC population, which usually starts to drop within 6 weeks of therapy. 19,23,26 In some cases, the frequencies of MDSC in HIV patients with HAART were comparable to healthy controls. 20 The decrease in stimuli due to viral suppression by ART/HAART might be attributed to the drop in the level of MDSC.…”

Section: The Effect Of Art/haarton Mdscsmentioning

confidence: 86%

“…25 In SIV infected rhesus macaques, gMDSCs were shown to be the dominant MDSCs comprising a median 90% of the total MDSC population over the course of SIV infection. 26 A report from Agrati et al also showed that HIV disease progression correlates with an increase in gMDSC subsets. 27 In the same study, 27 despite an expansion of gMDSCs, HIV patients with low gMDSC frequency (<6%) had a higher HIV DNA level than individuals with high gMDSC frequency (>6%), suggesting that gMDSC might interfere with HIV reservoir establishment.…”

Section: Gmdscs During Hiv Infectionmentioning

confidence: 95%

See 1 more Smart Citation

<p>Paradoxes in the Phenotype, Frequency and Roles of Myeloid-Derived Suppressor Cells During HIV Infection</p>

Ademe¹

2020

HIV

View full text Add to dashboard Cite

Myeloid-derived suppressor cells (MDSCs) are heterogeneous groups of pathologically activated myeloid cells with potent immunosuppressive function. Due to their role in negatively regulating the immune system, MDSCs have been strongly correlated with disease progression during HIV. However, findings vary considerably between studies. The dominant phenotype of MDSC subsets during HIV is not well ascertained. Moreover, there is no clear understanding on the clinical significance of MDSCs during HIV infection. The existing evidences showed the double-sided roles of MDSCs in HIV. On the one hand, MDSCs are linked to deleterious effects during HIV infection as they inhibit proliferation of protective T cell response. On the other hand, the immunosuppressive abilities of MDSCs were shown to be beneficial in curbing the damaging effects of persistent immune activation associated with chronic HIV infection. Therefore, this review aimed to describe the differences in the existing literatures pertaining to the phenotype, frequency and roles of MDSCs during HIV infection.

show abstract

Section: The Effect Of Art/haarton Mdscsmentioning

confidence: 86%

Section: Gmdscs During Hiv Infectionmentioning

confidence: 95%

<p>Paradoxes in the Phenotype, Frequency and Roles of Myeloid-Derived Suppressor Cells During HIV Infection</p>

Ademe¹

2020

HIV

View full text Add to dashboard Cite

show abstract

“…The immunosuppressive potential of PMN-MDSCs has been described in an oncology context [1][2][3][4][5][6][7] and more recently in infectious diseases [8][9][10][11]. PMN-MDSCs were shown to accumulate in chronic HIV infection [8,12]. Significantly higher numbers of PMN-MDSCs have been found in untreated patients with progressive HIV infection (progressors = PR) than in HIV-uninfected/healthy controls (HC), HIV controllers (CO) or antiretroviral-treated patients [8,13].…”

Section: Introductionmentioning

confidence: 99%

High frequencies of PMN-MDSCs are associated with low suppressive capacity in advanced stages of HIV-1 infection

et al. 2020

View full text Add to dashboard Cite

Background: Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are an immature cell type that inhibits the effector functions of T lymphocytes in chronic HIV infection. A well-known immunological feature of the disease course is the development of immune exhaustion, which is correlated with excessive immune activation in late-stage disease. Here, we hypothesized that immune exhaustion would also affect PMN-MDSCs in late-stage HIV-1 infection. Methods: We evaluated untreated chronically HIV-infected patients (progressors, n = 10) and control groups (controllers, patients with non-small cell lung carcinoma and healthy controls, n = 16) with regard to levels of PMN-MDSCs and their inhibitory potential. Additionally, we studied CD8 T cell effector functions (interferon-gamma, TNF alpha, IL-2 and CD107) and parameters of CD8 T cell activation (CD38 and HLA-DR) and exhaustion (PD-1 and LAG-3) by flow cytometry. Plasma inflammation markers analyzed here were IL-6, IL-8, soluble CD14, highly sensitive CRP, and cystatin C. Results: Coincubation experiments with isolated PMN-MDSCs led to a significant inhibition of CD8 T cell proliferation (p < 0.0001), with a significant correlation between PMN-MDSC frequency and suppressive capacity: the higher the frequency of PMN-MDSCs was, the lower the suppressive capacity (rho = 0.51, p = 0.0082). Stratifying all study subjects into subgroups with PMN-MDSC frequencies above or below 2.5% resulted in a significantly increased suppressive capacity in patients with frequencies below 2.5% (p = 0.021). While there was no correlation with the cellular activation markers CD38 and HLA-DR, high IL-8 levels were significantly associated with high PMN-MDSC frequencies (rho = 0.52, p = 0.0074) and low suppressive capacity (rho = 0.47, p = 0.019). Conclusions: In this study, we demonstrate for the first time that PMN-MDSCs show limited effector functions in advanced disease stages of HIV infection. The hyperactive immune state is associated with this loss of function. However, we show an association with the proinflammatory cytokine IL-8, which is an important factor for the migration and adhesion of polymorphonuclear cells.

show abstract

“…ART decreases PMN-MDSC levels within 6 weeks ( 28 , 29 ). However, data on SIV-infected monkeys report a minor percentage of M-MDSCs within the complete MDSC population and higher levels of PMN-MDSCs during ART than that before infection ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

Treatment Intensification in HIV-Infected Patients Is Associated With Reduced Frequencies of Regulatory T Cells

et al. 2018

View full text Add to dashboard Cite

In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [=5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets. The New Era (NE) study recruited patients with primary HIV infection (PHI) or chronically HIV-infected patients with conventional ART (CHI) and applied an intensified 5-drug regimen containing maraviroc and raltegravir for several years. We compared the frequencies of the immune suppressive cells, namely, the myeloid-derived suppressor cells (MDSCs), regulatory B cells (Bregs), and regulatory T cells (Tregs), of the treatment intensification patients to the control groups, especially to the patients with conventional 3-drug ART, and analyzed the Gag/Nef-specific CD8 T cell responses. There were no differences between PHI and CHI in the NE population (p > 0.11) for any of the studied cell types. Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic myeloid-derived suppressor cell (M-MDSC), and the Breg frequencies were comparable to those of patients with a 3-drug ART. However, the Treg levels were significantly lower in the NE patients than those in 3ART-treated individuals and other control groups (p ≤ 0.0033). The Gag/Nef-specific CD8 T cell response was broader (p = 0.0134) with a higher magnitude (p = 0.026) in the NE population than that in the patients with conventional ART. However, we did not find a correlation between the frequency of the immune suppressive cells and the interferon-gamma+ CD8 T cell response. In the treatment intensification subjects, the frequencies of the immune suppressive cells were comparable or lower than those of the conventional ART-treated subjects, with surprisingly broad HIV-specific CD8 T cell responses, suggesting a preservation of immune function with the applied treatment regimen. Interestingly, these effects were seen in both treatment intensification subpopulations and were not attributed to the start of treatment in primary infection.

show abstract

Kinetics of Myeloid-Derived Suppressor Cell Frequency and Function during Simian Immunodeficiency Virus Infection, Combination Antiretroviral Therapy, and Treatment Interruption

Cited by 24 publications

References 35 publications

<p>Paradoxes in the Phenotype, Frequency and Roles of Myeloid-Derived Suppressor Cells During HIV Infection</p>

<p>Paradoxes in the Phenotype, Frequency and Roles of Myeloid-Derived Suppressor Cells During HIV Infection</p>

High frequencies of PMN-MDSCs are associated with low suppressive capacity in advanced stages of HIV-1 infection

Treatment Intensification in HIV-Infected Patients Is Associated With Reduced Frequencies of Regulatory T Cells

Contact Info

Product

Resources

About