Differential expression of CD96 surface molecule represents CD8⁺ T cells with dissimilar effector function during HIV-1 infection

During HIV-1 infection, immune dysregulation and aberrant lymphocyte functions are well-established characteristics. Cell surface molecules are important for immunological functions and changes in expression can affect lymphocyte effector functions, thereby contributing to pathogenesis and disease p...

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Veröffentlicht in:PloS one 2012-12, Vol.7 (12), p.e51696
Hauptverfasser: Eriksson, Emily M, Keh, Chris E, Deeks, Steven G, Martin, Jeffrey N, Hecht, Frederick M, Nixon, Douglas F
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Keh, Chris E
Deeks, Steven G
Martin, Jeffrey N
Hecht, Frederick M
Nixon, Douglas F
description During HIV-1 infection, immune dysregulation and aberrant lymphocyte functions are well-established characteristics. Cell surface molecules are important for immunological functions and changes in expression can affect lymphocyte effector functions, thereby contributing to pathogenesis and disease progression. In this study we have focused on CD96, a member of the IgG superfamily receptors that have generated increasing recent interest due to their adhesive and co-stimulatory functions in addition to immunoregulatory capacity. CD96 is expressed by both T and NK cells. Although the function of CD96 is not completely elucidated, it has been shown to have adhesive functions and enhance cytotoxicity. Interestingly, CD96 may also have inhibitory functions due to its immunoreceptor tyrosine-based inhibitory motif (ITIM). The clinical significance of CD96 is still comparatively limited although it has been associated with chronic Hepatitis B infection and disease progression. CD96 has not previously been studied in the context of HIV-1 infection, but due to its potential importance in immune regulation and relevance to chronic disease, we examined CD96 expression in relation to HIV-1 pathogenesis. In a cross-sectional analysis, we investigated the CD8(+) T cell expression of CD96 in cohorts of untreated HIV-1 infected adults with high viral loads (non-controllers) and low viral loads ("elite" controllers). We demonstrated that elite controllers have significantly higher CD96 mean fluorescence intensity on CD8(+) T cells compared to HIV-1 non-controllers and CD96 expression was positively associated with CD4(+) T cell counts. Functional assessment showed that CD8(+) T cells lacking CD96 expression represented a population that produced both perforin and IFN-γ following stimulation. Furthermore, CD96 expression on CD8(+) T cells was decreased in presence of lipopolysaccharide in vitro. Overall, these findings indicate that down-regulation of CD96 is an important aspect of HIV-1 pathogenesis and differential expression is related to cell effector functions and HIV-1 disease course.
doi_str_mv 10.1371/journal.pone.0051696
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Cell surface molecules are important for immunological functions and changes in expression can affect lymphocyte effector functions, thereby contributing to pathogenesis and disease progression. In this study we have focused on CD96, a member of the IgG superfamily receptors that have generated increasing recent interest due to their adhesive and co-stimulatory functions in addition to immunoregulatory capacity. CD96 is expressed by both T and NK cells. Although the function of CD96 is not completely elucidated, it has been shown to have adhesive functions and enhance cytotoxicity. Interestingly, CD96 may also have inhibitory functions due to its immunoreceptor tyrosine-based inhibitory motif (ITIM). The clinical significance of CD96 is still comparatively limited although it has been associated with chronic Hepatitis B infection and disease progression. CD96 has not previously been studied in the context of HIV-1 infection, but due to its potential importance in immune regulation and relevance to chronic disease, we examined CD96 expression in relation to HIV-1 pathogenesis. In a cross-sectional analysis, we investigated the CD8(+) T cell expression of CD96 in cohorts of untreated HIV-1 infected adults with high viral loads (non-controllers) and low viral loads ("elite" controllers). We demonstrated that elite controllers have significantly higher CD96 mean fluorescence intensity on CD8(+) T cells compared to HIV-1 non-controllers and CD96 expression was positively associated with CD4(+) T cell counts. Functional assessment showed that CD8(+) T cells lacking CD96 expression represented a population that produced both perforin and IFN-γ following stimulation. Furthermore, CD96 expression on CD8(+) T cells was decreased in presence of lipopolysaccharide in vitro. Overall, these findings indicate that down-regulation of CD96 is an important aspect of HIV-1 pathogenesis and differential expression is related to cell effector functions and HIV-1 disease course.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23272144</pmid><doi>10.1371/journal.pone.0051696</doi><oa>free_for_read</oa></addata></record>
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subjects Aberration
Acquired immune deficiency syndrome
Adults
AIDS
Antigens
Antigens, CD - metabolism
Biology
Blood & organ donations
CD4 antigen
CD4 Lymphocyte Count
CD8 antigen
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cell Differentiation - immunology
Cell surface
Chronic illnesses
Chronic infection
Cloning
Control
Controllers
Cytotoxicity
Disease Progression
Down-Regulation
Effector cells
Fluorescence
Gene Expression Regulation
Hepatitis
Hepatitis B
HIV
HIV Infections - immunology
HIV Infections - metabolism
HIV-1 - immunology
Human immunodeficiency virus
Humans
Immunoglobulin G
Immunology
Immunoreceptor tyrosine-based inhibition motif
Immunoregulation
Infections
Interferon
Interferon-gamma - biosynthesis
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - metabolism
Lipopolysaccharides
Lipopolysaccharides - immunology
Lymphocytes
Lymphocytes T
Medicine
Pathogenesis
Perforin
Perforin - biosynthesis
Receptors
Studies
T cell receptors
Toxicity
Tyrosine
γ-Interferon
title Differential expression of CD96 surface molecule represents CD8⁺ T cells with dissimilar effector function during HIV-1 infection
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