Expression of CD69 on T-cells from HIV-1-infected children and adolescents increases with increasing viral load

Böhler, Thomas; Walcher, Judith; Hölzl-Wenig, Gabi; Schnitzler, Paul; Geiss, Magdalena; Buchholz, B.; Linde, R.; Rütschle, H; Debatin, Klaus‐Michael

doi:10.1007/s004310051167

Cited by 13 publications

(8 citation statements)

References 22 publications

(30 reference statements)

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“…In our present study, the levels of CD69 expression on CD3+ subsets did not differ between the HIV positive and HIV negative control groups. This supports the observation by Krowka et al and Böhler et al [53, 54] that unstimulated T-cells from HIV- infected and negative control individuals exhibited similar levels of CD69 expression [53, 54]. The reduced proportions of T-lymphocytes coexpressing CD69 were seen only upon mitogen stimulation in HIV-infected adults [53].…”

Section: Discussionsupporting

confidence: 85%

Aflatoxin-Related Immune Dysfunction in Health and in Human Immunodeficiency Virus Disease

Jiang

Jolly

Preko³

et al. 2008

Clinical and Developmental Immunology

114

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Both aflatoxin and the human immunodeficiency virus (HIV) cause immune suppression and millions of HIV-infected people in developing countries are chronically exposed to aflatoxin in their diets. We investigated the possible interaction of aflatoxin and HIV on immune suppression by comparing immune parameters in 116 HIV positive and 80 aged-matched HIV negative Ghanaians with high (≥0.91 pmol/mg albumin) and low (<0.91 pmol/mg albumin) aflatoxin B1 albumin adduct (AF-ALB) levels. AF-ALB levels and HIV viral load were measured in plasma and the percentages of leukocyte immunophenotypes and cytokine expression were determined using flow cytometry. The cross-sectional comparisons found that (1) among both HIV positive and negative participants, high AF-ALB was associated with lower perforin expression on CD8+ T-cells (P = .012); (2) HIV positive participants with high AF-ALB had significantly lower percentages of CD4+ T regulatory cells (Tregs; P = .009) and naive CD4+ T cells (P = .029) compared to HIV positive participants with low AF-ALB; and (3) HIV positive participants with high AF-ALB had a significantly reduced percentage of B-cells (P = .03) compared to those with low AF-ALB. High AF-ALB appeared to accentuate some HIV associated changes in T-cell phenotypes and in B-cells in HIV positive participants.

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Section: Discussionsupporting

confidence: 85%

Aflatoxin-Related Immune Dysfunction in Health and in Human Immunodeficiency Virus Disease

Jiang

Jolly

Preko³

et al. 2008

Clinical and Developmental Immunology

114

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“…Though CD69 is rapidly expressed in viral infections (17)(18)(19), its role in the immune response to these infections has never been studied to date. We aimed at analyzing the effect of CD69 deficiency on the course of VACV infection, and we found that CD69 deficiency results in increased early NK cell-dependent control of the infection.…”

mentioning

confidence: 99%

CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis

Notario

Alari-Pahissa

Molina

et al. 2016

J Virol

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During the host response to viral infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postinfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69 ؊/؊ mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69 ؊/؊ lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV infection at least in part through cell homeostatic survival. IMPORTANCEWe show that increased natural killer (NK) cell numbers augment the host response and survival after infection with vaccinia virus. This phenotype is found in the absence of CD69 in immunocompetent and immunodeficient hosts. As part of the innate immune system, NK lymphocytes are activated and participate in the defense against infection. Several studies have focused on the contribution of NK cells to protection against infection with vaccinia virus. In this study, it was demonstrated that the augmented early NK cell response in the absence of CD69 is responsible for the increased protection seen during infection with vaccinia virus even at late times of infection. This work indicates that the CD69 molecule may be a target of therapy to augment the response to poxvirus infection. V accinia virus (VACV) is a member of the Poxviridae family and was used as a vaccine to eradicate the variola virus, which is from the same family. Since then, it has commonly been used in research as a vaccine vector model. It is a large DNA virus with a linear double-stranded DNA genome that encodes Ͻ200 proteins (1). It has a broad cellular tropism and infects almost any cell line in culture. Members of this virus family do not usually establish persistent or latent infections and have a low mutation rate (2). VACV infection is initially controlled by the innate immune response, but it can be eradicated only by adaptive immunity, and Rag Ϫ/Ϫ mice finally succumb to the infection (3). Natural killer (NK) cells are crucial players in the first line of defense against viral infections. Through their expression of a range of germ line-encoded receptors, they are able to recognize v...

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“…CD69 has been found to be rapidly upregulated on all the leukocyte lineages studied, upon activation with the corresponding stimuli (14). CD69 expression has also been reported in infections (32)(33)(34)(35). Earlier studies showed that CD69 regulates the immune response by modulating the expression of various cytokines.…”

Section: Discussionmentioning

confidence: 86%

Epstein-Barr virus latent membrane protein 1 induces CD69 expression through activation of nuclear factor-κB

Ishikawa

Mori

2013

International Journal of Oncology

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Latent membrane protein‑1 (LMP-1) of Epstein‑Barr virus (EBV) promotes tumorigenesis. Here, we report that LMP-1 activates the immunoregulatory molecule CD69 gene transcription through a nuclear factor-κB (NF-κB)‑dependent pathway. CD69 expression was upregulated in LMP-1‑expressing EBV-immortalized human B-cell lines and an EBV-positive Burkitt's lymphoma cell line. LMP-1 expression increased CD69 expression at the transcriptional level. CD69 promoter was regulated by LMP-1 activation of NF-κB via the carboxy-terminal activation region 1 and 2. Promoter deletion analysis indicated that two NF-κB binding sites are necessary for activation of the CD69 promoter. Electrophoretic mobility shift analysis demonstrated that LMP-1 activates both NF-κB binding sites in the CD69 promoter. This is the first report of the regulation of CD69 expression by LMP-1, and this novel finding may, thus, represent an important link between the EBV oncoprotein LMP-1 and its critical role in the development of EBV-associated diseases.

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Expression of CD69 on T-cells from HIV-1-infected children and adolescents increases with increasing viral load

Cited by 13 publications

References 22 publications

Aflatoxin-Related Immune Dysfunction in Health and in Human Immunodeficiency Virus Disease

Aflatoxin-Related Immune Dysfunction in Health and in Human Immunodeficiency Virus Disease

CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis

Epstein-Barr virus latent membrane protein 1 induces CD69 expression through activation of nuclear factor-κB

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