Virus load correlates inversely with the expression of cytotoxic T lymphocyte activation markers in HIV-1-infected/AIDS patients showing MHC-unrestricted CTL-mediated lysis

Sindhu, Sardar; Ahmad, Rasheed; Blagdon, Marie; Ahmad, Ali; Toma, Emil; Morisset, R; Menezes, José

doi:10.1046/j.1365-2249.2003.02120.x

Cited by 8 publications

(4 citation statements)

References 30 publications

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“…Hence, the disease progression was a result of the immune response to the virally infected CD4 cells. Loss of LTNP status in those individuals with CTLe activity may also be related to the pathogenic role that CTLs can play by lysing various types of immunoregulatory cells, thus contributing to immunosuppression and hastening progression of infection [Sindhu et al, 2003]. Although there is no direct evidence of CD4 þ T-lymphocyte reduction in those individuals with CTLe activity in this study, other investigators have shown some CTL subsets to eliminate CD4 þ T lymphocytes without major histocompatibility-restricted target recognition [Bienzle et al, 1996] causing immunopathology by destroying the bystander CD4 þ T lymphocytes in blood [Zarling et al, 1990;Grant et al, 1993].…”

Section: Discussionmentioning

confidence: 99%

Effector HIV‐specific cytotoxic T‐lymphocyte activity in long‐term nonprogressors: Associations with viral replication and progression

Keoshkerian

Ashton

Smith

et al. 2003

Journal of Medical Virology

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Ex vivo effector cytotoxic T-lymphocyte (CTL) activity was assessed in 27 members of the Australian Long-Term Nonprogressor cohort and correlated with genetic, virological, and immunological markers. The 27 individuals were antiretroviral naive with CD4(+) T-cell counts of >500 cells/ microl for more than 8 years after human immunodeficiency virus type 1 (HIV-1) infection. Effector CTL activity was determined using a standard ex vivo chromium release assay. Individuals with CTL activity (HIV-1 env(IIIB) or pol or gag) were then compared to those without CTL activity in relation to plasma HIV-1 RNA, ICD p24 antigen, beta(2)-microglobulin, CD4 and CD8 T-cell counts, CCR5 and CCR2b genotypes, and progression to CD4 <500 cells/microl or commencement of antiretroviral treatment. Of the 27 individuals examined, 19 had no detectable effector CTL activity. The eight individuals with detectable CTL activity had significantly higher plasma levels of HIV-1 RNA (P = 0.014), immune complex dissociated p24 antigen (P = 0.006), and beta(2)-microglobulin (P = 0.009). There was increased risk of progression within 4 years of study entry in individuals with detectable effector CTL activity, higher plasma levels of HIV-1 RNA, higher beta(2)-microglobulin levels, and higher immune complex dissociated p24 antigen levels at enrollment (P = 0.017, P = 0.004, P = 0.027, P = 0.008 respectively). Multivariate analysis demonstrated viral load remained the strongest predictor of disease progression within this group (P = 0.017). There were no significant associations between CTL response and chemokine receptor genotype. These findings demonstrate the importance of HIV replication in generating an effector CTL response and show that effector CTL activity may be an early predictor of progression in people with long-term asymptomatic HIV infection.

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Section: Discussionmentioning

confidence: 99%

Effector HIV‐specific cytotoxic T‐lymphocyte activity in long‐term nonprogressors: Associations with viral replication and progression

Keoshkerian

Ashton

Smith

et al. 2003

Journal of Medical Virology

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“…The blood samples were diluted 1: 2 with sterile physiological saline (pH 7.1) and PBMC were isolated using Ficoll-Hypaque density gradient method as described [16]. Primary monocytes were purified by negative selection and following the manufacturer’s instructions (Human monocyte isolation kit II, MACS Miltenyi Biotec GmbH, Germany).…”

Section: Methodsmentioning

confidence: 99%

Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

Sindhu

Akhter

Kochumon

et al. 2018

Cell Physiol Biochem

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Background/Aims: Metabolic diseases such as obesity and type-2 diabetes (T2D) are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. Methods: TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC), or primary monocytes were treated with hydrogen peroxide (H₂O₂) for induction of reactive oxygen species (ROS)-mediated oxidative stress. Superoxide dismutase (SOD) activity was measured using a commercial kit. Data (mean±SEM) were compared using unpaired student’s t-test and P<0.05 was considered significant. Results: The adipose tissue TLR10 gene/protein expression was found to be significantly upregulated in obesity as well as T2D which correlated with body mass index (BMI). ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB)/mitogen activated protein kinase (MAPK) signaling as well as endoplasmic reticulum (ER) stress. H₂O₂-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Conclusion: Oxidative stress induces the expression of TLR10 which may represent an immune marker for metabolic inflammation.

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“…This was shown by analyzing the relative CD38 mean flourescence intensity (MIF) of CD8þ T cells, where an increase in values is observed from control (7.4) to good and partial VLRs (14.7 and 15.3, respectively), and with a further increase in poor VLRs (22.9). In HIV-1 infected adults, the high expression of CD38 on CD8þ T cells has been associated with a poorer prognosis and/or lack of response to ART (38)(39)(40)(41)(42)(43)(44).…”

Section: Nk and B Cell Counts And Expression Of Cd5 On B Cells In Thementioning

confidence: 99%

HIV‐1‐infected children on HAART: Immunologic features of three different levels of viral suppression

Zaccarelli-Filho¹,

Ono²,

Machado³

et al. 2006

Cytometry Part B Clinical

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Background: HIV-1-infected children show changes of blood lymphocyte subpopulations. We have, therefore, investigated how highly active anti-retroviral therapy (ART) alter these subsets. Blood samples were taken from 41 HIV-1-infected children on ART who were divided into groups showing good, partial and poor responses to ART on the basis of viral load (VL) measurement in blood. The observations were compared to those seen in 20 uninfected children.Methods: The samples were studied using 4-color flow cytometry for ''naïve'', central memory and effector memory cells as well as for CD38 expression as the sign of activation within both the CD4+ and the CD8+ T cell populations. HIV-1 infected children were also evaluated for the presence and the titers of antibodies induced by vaccination against childhood infections in our patients while on HAART.Results: Lymphocyte counts were lower in the \poor" viral load responding (VLR) group when compared with partial and good VLRs. Poor VLRs had lower total and naïve CD4+ T cell counts. HIV-1-infected children from all three groups had high CD8+ T cell counts. Central memory CD4+ and CD8+ T cell percentages were particularly low in the poor VLR group while in the poor VLR group the percentages of effector memory CD4+ and CD8+ T cells were higher when compared with the control group. Higher cellular activation of CD8+ T cells was observed in HIV-1-infected children, particularly when analyzed for the intensity of CD38 expression in the poor VLR group. CD5 expression on B cells was higher among all HIV-1-infected children. Antibodies to tetanus, diphtheria, measles, rubella, and hepatitis B were present in a large proportion of children but the titers were similarly low for all three groups of HIV-infected children.Conclusions: Children with different levels of viral response to HAART present immune phenotype characteristics that tend to place the children with partial and good virological responses into the same group. These children are still moderately deficient in their immune responses but show better recovery than seen with children in the poor VLR group. These observations indicate that the proportions of central memory cells among the CD4+ T cells and the intensity of the expression of CD38 activation antigen on CD8+ T cells provide more informative parameters for monitoring children on HAART than the absolute numbers of CD4+ and CD8+ T cells alone. q

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Virus load correlates inversely with the expression of cytotoxic T lymphocyte activation markers in HIV-1-infected/AIDS patients showing MHC-unrestricted CTL-mediated lysis

Cited by 8 publications

References 30 publications

Effector HIV‐specific cytotoxic T‐lymphocyte activity in long‐term nonprogressors: Associations with viral replication and progression

Effector HIV‐specific cytotoxic T‐lymphocyte activity in long‐term nonprogressors: Associations with viral replication and progression

Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

HIV‐1‐infected children on HAART: Immunologic features of three different levels of viral suppression

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