scholarly journals Nuclear Factor of Activated T Cells and Cytokines Gene Expression of the T Cells in AIDS Patients with Immune Reconstitution Inflammatory Syndrome during Highly Active Antiretroviral Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jia Sun ◽  
Heling Chen ◽  
Yirui Xie ◽  
Junwei Su ◽  
Ying Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Highly Active Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
High Expression ◽  
Nuclear Factor ◽  
Aids Patients ◽  
Activated T Cells ◽  
Inflammatory Syndrome

Background. The etiology of immune reconstitution inflammatory syndrome (IRIS) in AIDS patients after the initiation of HAART remains unknown. Several researches indicated that the development of IRIS is associated with the production and variation of cytokines, whose gene expression are closely related to the Ca2+/CN-nuclear factor of activated T cells (NFAT) pathway.Methods. We studied the expression of NFAT isoforms and their major target cytokines genes in peripheral blood CD3+T cells of subjects through fluorescence quantitative PCR and explored the expression changes of these genes before and after HAART.Results. After the initiation of HARRT, NFAT1, IL-6, and IL-8 gene expression showed a reversal trend in the CD3+T cells of the IRIS group and changed from low expression before HARRT to high expression after HARRT. In particular, the relative gene expression of NFAT1 was markedly higher compared with the other three isoforms. The IRIS group also showed higher NFAT4, NFAT2, NFAT1, IL-1β, IL-10, IL-2, IL-18, and TNF-αgene expression than the non-IRIS group.Conclusion. This study suggested that high expression levels of IL-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, IL-12, and IL-18 can predict the risk of IRIS. The increased expression of NFAT1 and NFAT4 may promote the expression of cytokines, such as IL-6, IL-8, and TNF-α, which may promote the occurrence of IRIS.

scholarly journals Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

2012 ◽  
Vol 54 (4) ◽  
pp. 231-233 ◽  
Author(s):  
Walter de Araujo Eyer-Silva ◽  
Maria Cecília da Fonseca Salgado ◽  
Jorge Francisco da Cunha Pinto ◽  
Fernando Raphael de Almeida Ferry ◽  
Rogério Neves-Motta ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Highly Active Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
Gouty Arthritis ◽  
Infected Male ◽  
Acute Gouty Arthritis ◽  
Highly Active ◽  
History Of ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

scholarly journals STIM2 targets Orai1/STIM1 to the AKAP79 signaling complex and confers coupling of Ca2+entry with NFAT1 activation

2020 ◽  
Vol 117 (28) ◽  
pp. 16638-16648 ◽  
Author(s):  
Ga-Yeon Son ◽  
Krishna Prasad Subedi ◽  
Hwei Ling Ong ◽  
Lucile Noyer ◽  
Hassan Saadi ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Unique Role ◽  
Signaling Complex ◽  
Contact Sites ◽  
Channel Function

The Orai1 channel is regulated by stromal interaction molecules STIM1 and STIM2 within endoplasmic reticulum (ER)-plasma membrane (PM) contact sites. Ca2+signals generated by Orai1 activate Ca2+-dependent gene expression. When compared with STIM1, STIM2 is a weak activator of Orai1, but it has been suggested to have a unique role in nuclear factor of activated T cells 1 (NFAT1) activation triggered by Orai1-mediated Ca2+entry. In this study, we examined the contribution of STIM2 in NFAT1 activation. We report that STIM2 recruitment of Orai1/STIM1 to ER-PM junctions in response to depletion of ER-Ca2+promotes assembly of the channel with AKAP79 to form a signaling complex that couples Orai1 channel function to the activation of NFAT1. Knockdown of STIM2 expression had relatively little effect on Orai1/STIM1 clustering or local and global [Ca2+]iincreases but significantly attenuated NFAT1 activation and assembly of Orai1 with AKAP79. STIM1ΔK, which lacks the PIP2-binding polybasic domain, was recruited to ER-PM junctions following ER-Ca2+depletion by binding to Orai1 and caused local and global [Ca2+]iincreases comparable to those induced by STIM1 activation of Orai1. However, in contrast to STIM1, STIM1ΔK induced less NFAT1 activation and attenuated the association of Orai1 with STIM2 and AKAP79. Orai1-AKAP79 interaction and NFAT1 activation were recovered by coexpressing STIM2 with STIM1ΔK. Replacing the PIP2-binding domain of STIM1 with that of STIM2 eliminated the requirement of STIM2 for NFAT1 activation. Together, these data demonstrate an important role for STIM2 in coupling Orai1-mediated Ca2+influx to NFAT1 activation.

Orbital non-HIV immune reconstitution inflammatory syndrome after cytapheresis

2020 ◽  
pp. 112067212091933
Author(s):  
Jeremy Chiabo ◽  
Sacha Nahon-Esteve ◽  
Mohamed Alketbi ◽  
Sandra Lassalle ◽  
Nathalie Tieulie ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Highly Active Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
Highly Active ◽  
First Case ◽  
Neutropenic Patients ◽  
Mantel Cell Lymphoma ◽  
Intravenous Steroids ◽  
Inflammatory Syndrome ◽  
Work Up

The immune reconstitution inflammatory syndrome is a phenomenon typically described in HIV patient during the restoration of CD4 count after highly active antiretroviral therapy. Non-HIV immune reconstitution inflammatory syndrome has also been described after organ transplantation or immune recovery in neutropenic patients. We report the case of a 50-year-old man who presented to our department with left painful proptosis and ophthalmoplegia 2 days after having performed cytapheresis for a mantel cell lymphoma. Systemic work up and biopsy were performed and symptoms were relieved with intravenous steroids therapy. To our knowledge, this is the first case of orbital non-HIV immune reconstitution inflammatory syndrome described in the literature.

scholarly journals Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing immune reconstitution inflammatory syndrome

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3818-3827 ◽  
Author(s):  
Lis R. V. Antonelli ◽  
Yolanda Mahnke ◽  
Jessica N. Hodge ◽  
Brian O. Porter ◽  
Daniel L. Barber ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Cd4 T Cells ◽  
Immune Reconstitution ◽  
Interferon Γ ◽  
Effector Memory ◽  
Hiv Patients ◽  
Inflammatory Syndrome

Abstract Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in the treatment of HIV-infected patients. To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of antiretroviral therapy. Patients developing IRIS episodes displayed higher frequencies of effector memory, PD-1+, HLA-DR+, and Ki67+ CD4+ T cells than patients without IRIS. Moreover, PD-1+ CD4+ T cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. Elevated PD-1 and Ki67 expression was also seen in regulatory T cells of IRIS patients. Furthermore, IRIS patients displayed higher serum interferon-γ, compared with non-IRIS patients, near the time of their IRIS events and higher serum interleukin-7 levels, suggesting that the T-cell populations are also exposed to augmented homeostatic signals. In conclusion, our findings indicate that IRIS appears to be a predominantly CD4-mediated phenomenon with reconstituting effector and regulatory T cells showing evidence of increased activation from antigenic exposure. These studies are registered online at http://clinicaltrials.gov as NCT00557570 and NCT00286767.

scholarly journals A potential role for nuclear factor of activated T-cells in receptor tyrosine kinase and G-protein-coupled receptor agonist-induced cell proliferation

2002 ◽  
Vol 368 (1) ◽  
pp. 183-190 ◽  
Author(s):  
Chandrahasa R. YELLATURU ◽  
Salil K. GHOSH ◽  
R.K. RAO ◽  
Lisa K. JENNINGS ◽  
Aviv HASSID ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dna Synthesis ◽  
G Protein ◽  
Receptor Tyrosine Kinase ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Dna Binding Activity ◽  
G Protein Coupled

We have studied the role of nuclear factor of activated T-cells (NFAT) transcription factors in the induction of vascular smooth muscle cell (VSMC) growth by platelet-derived growth factor-BB (PDGF-BB) and thrombin, the receptor tyrosine kinase (RTK) and G-protein-coupled receptor (GPCR) agonists, respectively. NFATc1 but not NFATc2 or NFATc3 was translocated from the cytoplasm to the nucleus upon treatment of VSMCs with PDGF-BB or thrombin. Translocation of NFATc1 was followed by an increase in NFAT—DNA binding activity and NFAT-dependent reporter gene expression. Cyclosporin A (CsA), a potent and specific inhibitor of calcineurin, a calcium/calmodulin-dependent serine phosphatase involved in the dephosphorylation and activation of NFATs, blocked NFAT—DNA binding activity and NFAT-dependent reporter gene expression induced by PDGF-BB and thrombin. CsA also completely inhibited PDGF-BB- and thrombin-induced VSMC growth, as measured by DNA synthesis and cell number. In addition, forced expression of the NFAT-competing peptide VIVIT for calcineurin binding significantly attenuated the DNA synthesis induced by PDGF-BB and thrombin in VSMCs. Together, these findings for the first time demonstrate a role for NFATs in RTK and GPCR agonist-induced growth in VSMCs.

scholarly journals HIV-Associated Cryptococcal Immune Reconstitution Inflammatory Syndrome is Associated with Aberrant T Cell Function and Increased Cytokine Responses

2019 ◽  
Author(s):  
David B. Meya ◽  
Samuel Okurut ◽  
Godfrey Zziwa ◽  
Stephen Cose ◽  
David R. Boulware ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Opportunistic Infection ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Cryptococcal Meningitis ◽  
Immune Reconstitution ◽  
T Cell Memory ◽  
Cell Memory ◽  
Cytokine Responses ◽  
Inflammatory Syndrome

Cryptococcal meningitis remains a significant opportunistic infection among HIV-infected patients, contributing 15%-20% of HIV-related mortality. A complication of initiating Antiretroviral therapy (ART) following opportunistic infection is Immune Reconstitution Inflammatory Syndrome (IRIS). IRIS afflicts 10-30% of HIV-infected patients with cryptococcal meningitis (CM), but its immunopathogenesis is poorly understood. We compared circulating T cell memory subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal capsule component, glucuronoxylomannan (GXM) elicited consistently lower frequencies of CD4+ and CD8+ T cell memory subsets expressing intracellular cytokines (IL-2, IFN-γ and IL-17) among subjects who subsequently developed CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8+ central memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated polyfunctional IL-2+/IL-17+ CD4+ T cells in patients with CM-IRIS. Moreover, CD8+ central and effector memory T cells from CM-IRIS subjects also demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. Thus, ART during CM elicits distinct differences in T cell cytokine production in response to cryptococcal antigens both prior to and during the development of IRIS, suggesting an immunologic foundation for the development of this morbid complication of CM infection.

scholarly journals HIV Populations Shift After Tuberculosis Associated Immune Reconstitution Inflammatory Syndrome: Implications For HIV Remission

2020 ◽  
Author(s):  
Camille Lange ◽  
Maura Manion ◽  
Natalie Lindo ◽  
Robert Gorelick ◽  
Ana Ortega-Villa ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Cd4 T Cells ◽  
Immune Reconstitution ◽  
Long Term Effects ◽  
Genetic Characteristics ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Infected Cells ◽  
Inflammatory Syndrome

Abstract Tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) is a serious complication of starting combination antiretroviral therapy (cART). TB-IRIS emerges early after cART initiation and is characterized by rapid expansions of TB-specific CD4+ T cells and high levels of inflammatory mediators driven by CD4+ T cells. The effects of TB-IRIS on HIV populations are unknown, but could result in profound expansion and elimination of HIV infected cells via cellular activation and acute inflammation. We investigated immediate and long-term effects of TB-IRIS on HIV infected cells with and without TB-IRIS. We measured plasma HIV RNA, cell-associated HIV RNA and HIV DNA levels and compared genetic characteristics of HIV populations after prolonged cART. We found that TB-IRIS was associated with more diverse HIV DNA populations and HIV reservoirs after IRIS were distinct from pre-therapy populations, suggesting that TB-IRIS can shape the HIV reservoir with detrimental implications for HIV remission strategies.

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