A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapy

Price, Patricia; Keane, N.M.; Lee, Silvia; Lim, Andrew; McKinnon, E.; French, Martyn A.

doi:10.1111/j.1365-2567.2006.02407.x

Cited by 13 publications

(11 citation statements)

References 43 publications

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“…Our findings of levels of PHA-induced, PBMC-derived IL-4 and IL-5 production in HIV-infected subjects that are significantly higher than those in healthy adult controls (with or without PD-1/PD-L1 blockade; Fig. 6) support previous observations of elevated Ig E levels and eosinophilia in HIV-infected subjects (2,11,12). A comparison of mitogen-and antigen-induced lymphoproliferative responses and TH-1/TH-2 cytokine production in the presence and absence of coinhibitory signaling blockade may lead to an improved functional immune measure for monitoring HIV disease progression or response to antiviral therapy and is the subject of further study.…”

Section: Discussionsupporting

confidence: 81%

Cryopreservation Decreases Receptor PD-1 and Ligand PD-L1 Coinhibitory Expression on Peripheral Blood Mononuclear Cell-Derived T Cells and Monocytes

Campbell

Tustin

Riedel

et al. 2009

Clin Vaccine Immunol

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Section: Discussionsupporting

confidence: 81%

Cryopreservation Decreases Receptor PD-1 and Ligand PD-L1 Coinhibitory Expression on Peripheral Blood Mononuclear Cell-Derived T Cells and Monocytes

Campbell

Tustin

Riedel

et al. 2009

Clin Vaccine Immunol

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“…The inverse relationship between immunoglobulin levels and IFN-g responses in HIV-infected patients on ART cannot simply be explained by a bias towards type (T) 2 cytokine production, because we have shown that IgE levels correlated inversely with mitogen-induced production of both IL-5 (T2) and IFN-g (T1) mRNA [39]. Weak positive correlations were also evident between levels of IFN-g, IL-4d2 (both T1), IL-4 and IL-5 (both T2) mRNA after mitogenic stimulation.…”

Section: Discussionmentioning

confidence: 77%

Susceptibility to opportunistic infections in HIV‐infected patients with increased CD4 T‐cell counts on antiretroviral therapy may be predicted by markers of dysfunctional effector memory CD4 T cells and B cells

et al. 2007

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ObjectivesHIV-infected patients responding to combination antiretroviral therapy (ART) after experiencing severe immunodeficiency may exhibit persistent immune defects and occasionally experience opportunistic infections (OIs) despite increased CD4 T-cell counts. The investigation of immune defects in such patients was examined in this study. Methods CD4 effector memory T-cell (T em -cell) function [assessed by blood cytomegalovirus (CMV)interferon-g (IFN-g) enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) counts] and B-cell dysregulation [assessed by serum immunoglobulin A (IgA) and IgE levels] were examined in 27 patients with increased CD4 T-cell counts after receiving ART for over 2 years. Two of these patients and one other had developed OIs on ART and are described in detail. ResultsSerum levels of IgA and IgE were higher than reference intervals (Po0.001) and CMV IFN-g ELISPOT counts were lower than those in non-HIV-infected controls (Po0.001) in the HIV-infected patients. Low CMV IFN-g ELISPOT counts were associated with high IgA levels (r 5 À 0.5, P 5 0.01, Spearman's correlation test) and segregated with high IgE levels (P 5 0.06, Fisher's test). CMV IFN-g ELISPOT counts and serum IgA and IgE levels did not change significantly over a median time of 35 (range 8-60) months after the first measurement, whereas CD4 T-cell counts increased. All three patients who experienced OIs had repeatedly low CMV IFN-g ELISPOT counts and increased serum levels of IgA and/or IgE. ConclusionLow CD4 T em -cell function and B-cell dysregulation are immune defects that may persist independently of changes in the CD4 T-cell count in HIV-1-infected patients responding to ART and are associated with an increased risk of developing an OI. Introduction HIV-1-infected patients receiving combination antiretroviral therapy (ART) who had a nadir CD4 T-cell count below 50 cells/mL may have persistent immune dysfunction despite increased CD4 T-cell counts [1][2][3][4]. A small proportion of such patients experience opportunistic infections (OIs) [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] [23,24]. High serum IgE levels are not associated with the production of allergen-specific IgE antibodies [25,26] and in some patients are associated with an immunodeficiency syndrome resembling hyper-IgE syndrome, where serum IgA levels may also be high [27]. Antiretroviral therapy only partly corrects the increased immunoglobulin production [28,29]. High serum IgA levels in HIV-infected patients receiving ART are associated with B-cell activation [29], but the fundamental cause and significance of these abnormalities remain unclear.Here, we describe the clinical and immunological findings in three HIV-infected patients who experienced recurrent or de novo Aspergillus fumigatus and/or Mycobacterium avium complex (MAC) infection whilst receiving long-term ART even though total CD4 T-cell counts had increased. We provide evidence that these patients had low CD4 T em -cell function associated with increased production of IgA a...

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“…We subsequently associated CMV/encephalitis IRD with high and rising levels of plasma IL-6 and sCD30 (133,134). At the time, this was associated with a Th2 cytokine environment, but subsequent data shed doubt on this interpretation of elevated sCD30 (111).…”

Section: Ird Manifested As CMV Retinitis or Viral Encephalomyelitis: mentioning

confidence: 96%

Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

et al. 2009

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SUMMARY Up to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathological characteristics of IRD associated with viral infections suggest different pathogenic mechanisms. For example, IRD associated with varicella-zoster virus or JC polyomavirus infection correlate with a CD8 T-cell response in the central nervous system. Exacerbations or de novo presentations of hepatitis associated with hepatitis C virus (HCV) infection following ART may also reflect restoration of pathogen-specific immune responses as titers of HCV-reactive antibodies rise in parallel with liver enzymes and plasma markers of T-cell activation. Correlations between immunological parameters assessed in longitudinal sample sets and clinical presentations are required to illuminate the diverse immunological scenarios described collectively as IRD. Here we present salient clinical features and review progress toward understanding their pathogeneses.

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A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapy

Cited by 13 publications

References 43 publications

Cryopreservation Decreases Receptor PD-1 and Ligand PD-L1 Coinhibitory Expression on Peripheral Blood Mononuclear Cell-Derived T Cells and Monocytes

Cryopreservation Decreases Receptor PD-1 and Ligand PD-L1 Coinhibitory Expression on Peripheral Blood Mononuclear Cell-Derived T Cells and Monocytes

Susceptibility to opportunistic infections in HIV‐infected patients with increased CD4 T‐cell counts on antiretroviral therapy may be predicted by markers of dysfunctional effector memory CD4 T cells and B cells

Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

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