Lower cytokine secretion ex vivo by natural killer T cells in HIV-infected individuals is associated with higher CD161 expression

Snyder‐Cappione, Jennifer; Loo, Christopher; Carvalho, Karina I.; Kuylenstierna, Carlotta; Deeks, Steven G.; Hecht, Frederick M.; Rosenberg, Michael; Sandberg, Johan K.; Kallas, Esper G.; Nixon, Douglas F.

doi:10.1097/qad.0b013e32832b5134

Cited by 35 publications

(49 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We collected approximately 100 ml of fresh blood from 12 healthy donors (six males and six females). We discriminated NKT cells via expression of CD3, vα24, and a CD1d-antigen loaded tetramer to ensure accurate gating[8], [9], [39] (Figure 1). …”

Section: Resultsmentioning

confidence: 99%

A Comprehensive Ex Vivo Functional Analysis of Human NKT Cells Reveals Production of MIP1-α and MIP1-β, a Lack of IL-17, and a Th1-Bias in Males

Snyder‐Cappione

Tincati²,

Eccles-James³

et al. 2010

PLoS ONE

View full text Add to dashboard Cite

NKT cells contribute to the modulation of immune responses and are believed to be important in the pathogenesis of autoimmune and infectious diseases, as well as cancer. Variations in the composite NKT cytokine response may determine individual disease susceptibility or severity. Due to low frequencies in peripheral blood, knowledge of the breadth of ex vivo human NKT cell functions has been limited. To bridge this gap, we studied highly purified NKT cells from PBMC of healthy donors and assessed the production of 27 effector functions using sensitive Elispot and multiplex bead assays. We found the ex vivo human NKT cell response is predominantly comprised of the chemokines MIP1-α, and MIP1-β as well as the Th1 cytokines IFN-γ and TNF-α. Although lower in magnitude, there was also significant production of IL-2, IL-4, and perforin after mitogen stimulation. Surprisingly, little/no IL-5, IL-6, IL-10, or IL-13 was detected, and no subjects' NKT cells produced IL-17. Comparison of the NKT functional profiles between age-matched male and female subjects revealed similar IL-4 responses, but higher frequencies of cells producing IFN-γ and MIP1-α, from males. There were no gender differences in the circulating NKT subset distribution. These findings implicate chemokines as a major mechanism by which NKT cells control responses in humans. In addition, the panoply of Th2 and Th17 cytokine secretion by NKT cells from healthy donors may not be as pronounced as previously believed. NKT cells may therefore contribute to the gender bias found in many diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

A Comprehensive Ex Vivo Functional Analysis of Human NKT Cells Reveals Production of MIP1-α and MIP1-β, a Lack of IL-17, and a Th1-Bias in Males

Snyder‐Cappione

Tincati²,

Eccles-James³

et al. 2010

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…In the context of HIV-1, early studies described the numerical decline of iNKT cells in chronic stages of infection (11–15). Furthermore, the residual iNKT cells in chronically HIV-1 infected patients have an exhausted phenotype with poor functionality (16–18), and in particular the CD4+ subset of the residual iNKT cells display viral-load driven activation (19). In SIV infection of non-human primates, a study comparing iNKT cells in AIDS-resistant mangabeys and susceptible macaques indicated that high iNKT cell levels and certain phenotypes of these cells were associated with slower disease progression (20).…”

Section: Introductionmentioning

confidence: 99%

Innate Invariant NKT Cell Recognition of HIV-1–Infected Dendritic Cells Is an Early Detection Mechanism Targeted by Viral Immune Evasion

Paquin‐Proulx

Gibbs

Bächle

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Invariant natural killer T (iNKT) cells are innate-like T cells that respond rapidly with a broad range of effector functions upon recognition of glycolipid antigens presented by CD1d. HIV-1 carries Nef- and Vpu-dependent mechanisms to interfere with CD1d surface expression, indirectly suggesting a role for iNKT cells in control of HIV-1 infection. Here, we investigated if iNKT cells can participate in the innate cell-mediated immune response to HIV-1. Infection of dendritic cells (DCs) with Nef- and Vpu-deficient HIV-1 induced upregulation of CD1d in a TLR7-dependent manner. Infection of DCs caused modulation of enzymes in the sphingolipid pathway and enhanced expression of the endogenous glucocylceramide antigen. Importantly, iNKT cells responded specifically to rare DCs productively infected with Nef- and Vpu-defective HIV-1. Transmitted founder viral isolates differed in their CD1d down-regulation capacity, suggesting that diverse strains may be differentially successful in inhibiting this pathway. Furthermore, both iNKT cells and DCs expressing CD1d and HIV-receptors resided in the female genital mucosa, a site where HIV-1 transmission occurs. Together, these findings suggest that innate iNKT cell sensing of HIV-1 infection in DCs is an early immune detection mechanism, which is independent of priming and adaptive recognition of viral antigen, and is actively targeted by Nef- and Vpu-dependent viral immune evasion mechanisms.

show abstract

“…8,27 In HIV-1 infection, many of these pathways have been shown to be dysregulated. 28,29 In addition, high levels of persistent immune activation characterize chronic viremic HIV-1 infection, and the levels of immune activation have been closely associated with CD4 T cell count decline and clinical HIV-1 disease progression. 20,21 In our investigation of changes in the NKT cell compartment in advanced HIV-1 clade C disease, we observed that significantly more NKT cells are activated in advanced HIV-1 disease, in particular in those individuals with low CD4 T cell counts <200 cells/ ml.…”

Section: Discussionmentioning

confidence: 99%

Impairment of CD1d-Restricted Natural Killer T Cells in Chronic HIV Type 1 Clade C Infection

Mureithi

Cohen

Moodley

et al. 2011

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Recent studies suggest that natural killer T (NKT) cells play a role in early antiviral pathogenesis and are rapidly depleted in chronic human immunodeficiency virus type 1 (HIV-1) clade B infection. We aimed to characterize the phenotypic and functional characteristics of NKT cells in HIV-1 clade C-infected Africans at different stages of HIV-1 disease. NKT cell frequencies, subsets, and ex vivo effector functions were assessed using multiparametric flow cytometry in a cross-sectional analysis of cryopreserved peripheral blood mononuclear cells from a cohort of 53 HIV-1 clade C chronically infected South African adults with CD4 T cell counts ranging from 94 to 839 cells/ml. We observed a significant decline of NKT cell numbers in advanced HIV-1 disease as well as activation and functional impairment of NKT cells in individuals with low CD4 T cell counts. The loss of NKT cells was largely driven by a reduction in the CD4 þ and CD4 -CD8 -NKT cell subsets in advanced disease. These findings demonstrate significant impairment of the NKT cell compartment in progressive HIV-1 clade C disease that might play an important role in the modulation of immune function in HIV-1 infection.

show abstract

Lower cytokine secretion ex vivo by natural killer T cells in HIV-infected individuals is associated with higher CD161 expression

Abstract: The ex-vivo Th1 responses of circulating NKT cells to CD1d-glycolipid complexes are impaired in HIV-infected patients. NKT cell functions may be progressively lost over time in HIV infection, and CD161 is implicated in the regulation of NKT cell responsiveness.

Cited by 35 publications

References 23 publications

A Comprehensive Ex Vivo Functional Analysis of Human NKT Cells Reveals Production of MIP1-α and MIP1-β, a Lack of IL-17, and a Th1-Bias in Males

A Comprehensive Ex Vivo Functional Analysis of Human NKT Cells Reveals Production of MIP1-α and MIP1-β, a Lack of IL-17, and a Th1-Bias in Males

Innate Invariant NKT Cell Recognition of HIV-1–Infected Dendritic Cells Is an Early Detection Mechanism Targeted by Viral Immune Evasion

Impairment of CD1d-Restricted Natural Killer T Cells in Chronic HIV Type 1 Clade C Infection

Contact Info

Product

Resources

About