HIV-mediated up-regulation of invariant chain (CD74) correlates with generalized immune activation in HIV+ subjects

HIV Nef-mediated up-regulation of invariant chain (Ii chain, also CD74) is presumed to play an active role in HIV immunopathogenesis. However, this has not been definitely ascertained. In order to help elucidate this hypothesis, Ii chain, CD4, HLA-DR and HLA-ABC expression was analyzed ex vivo in mo...

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Vydané v:Virus research Ročník 163; číslo 1; s. 380 - 384
Hlavní autori: Ghiglione, Yanina, Rodríguez, Ana María, De Candia, Cristian, Carobene, Mauricio, Benaroch, Philippe, Schindler, Michael, Salomón, Horacio, Turk, Gabriela
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Netherlands Elsevier B.V 01.01.2012
Predmet:
Acquired Immunodeficiency Syndrome - immunology
Acquired Immunodeficiency Syndrome - pathology
Acquired Immunodeficiency Syndrome - virology
ADP-ribosyl Cyclase 1 - analysis
antigen-presenting cells
Antigens, Differentiation, B-Lymphocyte - biosynthesis
B-Lymphocytes - chemistry
B-Lymphocytes - immunology
CD4 Lymphocyte Count
CD4-positive T-lymphocytes
CD4-Positive T-Lymphocytes - chemistry
CD4-Positive T-Lymphocytes - immunology
Cells, Cultured
Gene Expression Profiling
Histocompatibility Antigens Class II - biosynthesis
HIV
HIV - immunology
HIV - pathogenicity
HLA-DR Antigens - analysis
Human immunodeficiency virus
Humans
Immune hyperactivation
Invariant chain (CD74)
macrophages
Macrophages - immunology
Macrophages - virology
Membrane Glycoproteins - analysis
Nef
patients
Up-Regulation
Viral Load
HIV
Invariant chain (CD74)
Nef
Immune hyperactivation
ISSN:0168-1702, 1872-7492, 1872-7492
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Shrnutí:HIV Nef-mediated up-regulation of invariant chain (Ii chain, also CD74) is presumed to play an active role in HIV immunopathogenesis. However, this has not been definitely ascertained. In order to help elucidate this hypothesis, Ii chain, CD4, HLA-DR and HLA-ABC expression was analyzed ex vivo in monocyte-derived macrophages (MDMs) from HIV+ subjects. Viral load, CD4+ T cell count and immune activation were also determined in enrolled subjects. Correlations between these parameters and the modulation of cell surface molecules in infected cells were studied. Ii chain expression was found to be up-regulated in infected MDMs derived from all patients but one (median fold up-regulation 2.47±1.82 (range 0.87–7.36)). Moreover, the magnitude of Ii chain up-regulation significantly correlated with higher activation of B and CD4+ T cells (studied by HLA-DR and CD38 expression). On the other hand, lower HLA-ABC (i.e. stronger down-regulation) in infected MDMs was associated with higher CD4 counts. No correlation was observed between the magnitude of Ii chain up-regulation and the other Nef functions studied here. This is the first study reporting that Ii chain up-regulation occurs on naturally infected antigen presenting cells obtained directly from HIV+ subjects. Moreover, it is also shown that the magnitude of this up-regulation correlates with immune activation. This allows postulating an alternative hypothesis regarding the contribution of Ii chain up-regulation to HIV-mediated immune damage.
Bibliografia:http://dx.doi.org/10.1016/j.virusres.2011.09.011
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ISSN:0168-1702
1872-7492
1872-7492
DOI:10.1016/j.virusres.2011.09.011