Transforming growth factor-beta and suppression of humoral immune responses in HIV infection.

Kekow, Jörn; Wachsman, William; McCutchan, J. Allen; Gross, W. L.; Zachariah, Michael R.; Carson, Dennis A.; Lotz, Martin

doi:10.1172/jci115059

Cited by 79 publications

(43 citation statements)

References 33 publications

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“…Some pathogenic aspects described in these groups may, however, play a role in SV as well. First, TGF-overexpression is associated with cellular and humoral immunodeficiency [21,23]. In SV, infectious disease shows a high prevalence, in which TGF-may account, together with other factors including immunosuppression by therapy, for a high mortality rate [28].…”

Section: Discussionmentioning

confidence: 99%

“…The sensitivity of the TGF-bioassay was 300 pg/ml, while the TGF--ELISA was able to detect 10 pg/ml TGF-. The samples (both culture supernatant and plasma) were tested at different dilutions with and without transient acidification to activate latent TGF- [18,21,23]. The samples were acidified and neutralized after 30 min as described earlier [3].…”

Section: Isolation Of Cells and Culture Conditionsmentioning

confidence: 99%

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Transforming growth factor-beta (TGF-β) expression and interaction with proteinase 3 (PR3) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Csernok

Szymkowiak

Mistry

et al. 1996

Clinical and Experimental Immunology

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SUMMARYTGF-¯is a multifunctional cytokine modulating the onset and course of autoimmune diseases as shown in experimental models. The aim of this study was to investigate TGF-¯expression in ANCA-associated vasculitis (AAV), and the possible interactions of this cytokine with lysosomal enzymes identified as ANCA autoantigens (e.g. PR3). This included TGF-¯effects on the translocation of the lysosomal enzymes to the cell surface of polymorphonuclear neutrophils (PMN), and the presumed activation of non-bioactive, latent TGF-¯by these enzymes. Patients with various types of systemic vasculitis (SV) were studied, including three different types of AAV (Wegener's granulomatosis (WG), Churg-Strauß syndrome (CSS) and microscopic polyangiitis (MPA)). Regardless of the type of assay applied, the TGF-¯1 isoform was found to be overexpressed in SV, including AAV, and to correlate with disease activity as shown for WG. Mean TGF-¯1 plasma levels in AAV patients ranged from 8 . 9 ng/ml (WG) to 13 . 3 ng/ml (CSS) (control 4 . 2 ng/ml; P < 0 . 01), while TGF-¯2 levels were not elevated. Flow cytometry analysis showed TGF-¯1 to be a potent translocation factor for PR3 comparable to other neutrophilactivating factors such as IL-8. PR3 membrane expression on primed PMN increased by up to 51% after incubation with TGF-¯1. PR3 itself was revealed as a potent activator of latent TGF-¯, thus mediating bioeffects of this cytokine. These findings, together with other features of TGF-¯such as induction of angiogenesis and its strong chemotactic capacity, indicate that TGF-¯might serve as a proinflammatory factor in SV, especially in AAV.

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Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Cells and Culture Conditionsmentioning

confidence: 99%

Transforming growth factor-beta (TGF-β) expression and interaction with proteinase 3 (PR3) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Csernok

Szymkowiak

Mistry

et al. 1996

Clinical and Experimental Immunology

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“…However, overexpression of TGF-␤ can lead to the conversion of its protective functions to pathogenetic manifestations through its profound and broad inhibitory effects on different antiviral defense mechanisms. Thus, overproduction of TGF-␤ during HIV infection may contribute to noncyto- This deficiency correlates closely with increased TGF-␤ secretion by peripheral blood mononuclear cells (PBMC) from HIV ϩ donors (131). Antibodies to TGF-␤ neutralize the inhibitory effect of HIV ϩ culture supernatants on normal B cells and increases low proliferative responses by HIV ϩ cells.…”

Section: Tgf-␤ and Il-10 During Hiv-1 Infectionmentioning

confidence: 99%

Chronic Immune Activation Associated with Chronic Helminthic and Human Immunodeficiency Virus Infections: Role of Hyporesponsiveness and Anergy

2004

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Chronic immune activation is one of the hallmarks of human immunodeficiency virus (HIV) infection. It is present also, with very similar characteristics, in very large human populations infested with helminthic infections. We have tried to review the studies addressing the changes in the immune profiles and responses of hosts infected with either one of these two chronic infections. Not surprisingly, several of the immune derangements and impairments seen in HIV infection, and considered by many to be the “specific” effects of HIV, can be found in helminth-infected but HIV-noninfected individuals and can thus be accounted for by the chronic immune activation itself. A less appreciated element in chronic immune activation is the immune suppression and anergy which it may generate. Both HIV and helminth infections represent this aspect in a very wide and illustrative way. Different degrees of anergy and immune hyporesponsiveness are present in these infections and probably have far-reaching effects on the ability of the host to cope with these and other infections. Furthermore, they may have important practical implications, especially with regard to protective vaccinations against AIDS, for populations chronically infected with helminths and therefore widely anergic. The current knowledge of the mechanisms responsible for the generation of anergy by chronic immune activation is thoroughly reviewed

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“…Tat can also transactivate, in both infected and uninfected cells, the expression of cellular genes coding for cytokines, chemokines or their receptors, extracellular matrix molecules, and integrins (33,106,139,144,179,191 (97,196).…”

Section: Tat Protein Of Hiv-1: Release Uptake and Extracellular Funcmentioning

confidence: 99%

Angiogenic Effects of Extracellular Human Immunodeficiency Virus Type 1 Tat Protein and Its Role in the Pathogenesis of AIDS-Associated Kaposi's Sarcoma

2002

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The Tat protein of human immunodeficiency virus (HIV) type 1 is a transactivator of viral gene expression that is required for virus replication and spread. Moreover, Tat is released by acutely HIV-infected cells via a leaderless secretory pathway and in a biologically active form that exerts effects on both HIV-infected and uninfected cells from different organs and systems. This review focuses on the activities of extracellular Tat protein on endothelial cells, on angiogenesis, and on the pathogenesis of AIDS-associated angioproliferative diseases such as Kaposi's sarcoma. In particular, we discuss results from different groups indicating that Tat mimics the proangiogenic activities of extracellular matrix molecules and that it enhances the effects of angiogenic factors

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Transforming growth factor-beta and suppression of humoral immune responses in HIV infection.

Cited by 79 publications

References 33 publications

Transforming growth factor-beta (TGF-β) expression and interaction with proteinase 3 (PR3) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Transforming growth factor-beta (TGF-β) expression and interaction with proteinase 3 (PR3) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Chronic Immune Activation Associated with Chronic Helminthic and Human Immunodeficiency Virus Infections: Role of Hyporesponsiveness and Anergy

Angiogenic Effects of Extracellular Human Immunodeficiency Virus Type 1 Tat Protein and Its Role in the Pathogenesis of AIDS-Associated Kaposi's Sarcoma

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