CYTOKINE-INDUCED EXPRESSION OF CD1b MOLECULES BY PERIPHERAL BLOOD MONOCYTES: INFLUENCE OF 3′-AZIDO-3′-DEOXYTHYMIDINE

Giuliani, Alessandro; Tentori, Lucio; Pepponi, Rita; Porcelli, Steven A.; Aquino, Angelo; Orlando, Laura; Sugita, Masahiko; Brenner, Michael B.; Bonmassar, Enzo; Graziani, Grazia

doi:10.1006/phrs.1997.0130

Cited by 10 publications

(8 citation statements)

References 18 publications

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“…), and hybridized at 68°C for 1 h with a 32 P-labeled probe using the QuickHyb hybridization solution (Stratagene, Cambridge, United Kingdom). CD1b-specific transcripts were detected as previously described using as a probe a 266-bp cDNA fragment corresponding to the second exon of the CD1B gene, which encodes the first extracellular domain of the mature CD1b protein, designated ␣1 (11,19,26). The glyceraldehyde-3-phosphate dehydrogenase (GAPDH) probe, a 0.9-kb EcoRI fragment of the human GAPDH gene, was a generous gift from R. Dalla Favera (Department of Pathology, Columbia University, New York, N.Y.).…”

Section: Reagentsmentioning

confidence: 99%

“…Western blot analysis of cytosol and cell membrane preparations was performed using the rabbit polyclonal antiserum that recognizes the denatured form of CD1b protein (11). The results of one of two similar independent experiments (Fig.…”

Section: Western Blot Analysis Of the Influence Of Bcg On Induction Omentioning

confidence: 99%

“…These findings raise the question of whether BCG vaccination could produce self-limiting cellular and/or humoral signals with respect to CD1-dependent immunity, which could be a potential factor contributing to its limited efficacy in tuberculosis prevention. Rabbit polyclonal antiserum recognizing the denatured CD1b protein for Western blot analysis was obtained as previously described (11).…”

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Influence ofMycobacterium bovisBacillus Calmette Guérin on In Vitro Induction of CD1 Molecules in Human Adherent Mononuclear Cells

et al. 2001

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Nonpeptide antigens (including glycolipids of microbial origin) can be presented to T cells by CD1 molecules expressed on monocyte-derived dendritic cells. These HLA unrestricted responses appear to play a role in host immunity against Mycobacterium tuberculosis and other pathogenic bacteria. It is known that vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) has limited efficacy in many clinical settings, although the reasons for its inadequacy remain unclear. Here we have investigated the influence of BCG on the induction of CD1b on human monocytes by granulocyte-macrophage colony-stimulating factor (GM-CSF), which is believed to be the principal inducer of this antigen-presenting molecule. Although BCG alone led to a slight induction of CD1b expression, this agent reduced markedly the ability of GM-CSF to induce high levels of CD1b that were typically observed in uninfected cells. Inhibition of CD1b expression in BCG-infected monocytes was apparent at both the mRNA transcript and CD1b protein levels. Down-regulation of CD1b expression by BCG was mediated, at least in part, by one or more soluble factors and could not be reversed with high concentrations of GM-CSF or a variety of other cytokines. The present results suggest that BCG could diminish the efficiency of CD1-restricted T-cell responses against nonpeptide mycobacterial antigens by reducing CD1 expression on antigen-presenting cells. These findings have potential implications for understanding the nature of the immune response elicited by BCG in humans and suggest potential strategies that could be important for the development of better vaccines for the prevention of tuberculosis.Data from the world literature show that morbidity and mortality from mycobacterial infections are continuously increasing (3,9,17). This appears to be due not only to a higher transmission rate of the disease, especially in immunocompromised human immunodeficiency virus (HIV)-infected patients (2, 5), but also to the emergence of multidrug-resistant strains of Mycobacterium tuberculosis (17,21,25). Therefore, effective early vaccination of individuals at high risk for developing active tuberculosis has been targeted as an important approach for tuberculosis control. Vaccination against M. tuberculosis has been attempted on a large scale using Mycobacterium bovis bacillus Calmette-Guérin (BCG), a live attenuated strain. However, the results of clinical trials that enrolled an extraordinary number of cases immunized with BCG were not consistently appealing (24,29). A recent meta-analysis of the literature showed that the vaccine significantly reduces the risk of tuberculosis by an average of only 50% (4). The reasons why BCG does not provide optimal protection are not clear, since the organism is known to share a number of major histocompatibility complex (MHC)-restricted antigens with virulent M. tuberculosis and also activates ␥␦ T cells that may facilitate the responses of CD4 ϩ and CD8 ϩ responder T cells that are important in maintaining immunity to M. t...

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Section: Reagentsmentioning

confidence: 99%

Section: Western Blot Analysis Of the Influence Of Bcg On Induction Omentioning

confidence: 99%

mentioning

confidence: 99%

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Influence ofMycobacterium bovisBacillus Calmette Guérin on In Vitro Induction of CD1 Molecules in Human Adherent Mononuclear Cells

et al. 2001

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“…Previous studies performed in our laboratory have shown that the total amount of AMNC expressing CD1b molecule can be depressed by the antiviral agent 3'-azido-3'-deoxythymidine 21 . On the other hand, expression of the same antigen on AMNC can be up-regulated by rifampin 10,22 .…”

Section: Attempts To Reverse Bcg-mediated Impairment Of Cd1b Inductiomentioning

confidence: 99%

Bacillus Calmette-Guerin Down-Regulates CD1b Induction by Granulocyte-Macrophage Colony Stimulating Factor in Human Peripheral Blood Monocytes

Prete¹,

Giuliani²,

Iona³

et al. 2001

Journal of Chemotherapy

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Non-peptide antigens (e.g. glycolipids of microbial origin) presented by monocyte-associated CD1 molecules to T cells appear to play an important role in host immunity against tuberculosis and other pathogenic bacteria. Since vaccination with Bacillus Calmette-Guerin (BCG) has limited efficacy, the influence of viable BCG organisms on the induction of CD1b antigen by granulocyte macrophage-colony stimulating factor (GM-CSF) has been tested in adherent mononuclear cells obtained from peripheral blood of healthy donors. The results indicate that the vaccine reduces substantially CD1b induction by GM-CSF. On the other hand, BCG was found to promote a slight increase in the expression of this molecule on target cells not exposed to GM-CSF. Attempts to reverse the antagonistic effects of BCG on GM-CSF with high concentrations of GM-CSF, alone, or associated with IL-4, were unsuccessful. Moreover, mycobacteria suppression by 10 microg/ml of rifampin, did not affect BCG influence on CD1b induction. The present results suggest that mycobacterium-induced impairment of the CD1 system could play a role in the unsatisfactory results obtained with BCG vaccination.

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“…CD1a, CD1b, CD1c) resemble MHC class I antigenpresenting molecules as they associate with β 2 -microglobulin [5,8], bind lipids [13], and are expressed prominently on APC of the myeloid lineage, including DCs derived from circulating monocytes [14,15]. Adherent blood mononuclear cells (AMNC) can be activated by GM-CSF to express CD1 group 1 proteins [4,[16][17][18]. Activation is attained through GM-CSF binding to the alpha subunit of GM-CSF receptor (GM-CSF-R) on cell surface, followed by interaction with the intra-cytoplasmatic domain of receptor beta subunit responsible for signal transduction [19].…”

Section: Introductionmentioning

confidence: 99%

BCG-infected adherent mononuclear cells release cytokines that regulate group 1 CD1 molecule expression

Prete

Giuliani

D’Atri

et al. 2007

International Immunopharmacology

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CYTOKINE-INDUCED EXPRESSION OF CD1b MOLECULES BY PERIPHERAL BLOOD MONOCYTES: INFLUENCE OF 3′-AZIDO-3′-DEOXYTHYMIDINE

Cited by 10 publications

References 18 publications

Influence ofMycobacterium bovisBacillus Calmette Guérin on In Vitro Induction of CD1 Molecules in Human Adherent Mononuclear Cells

Influence ofMycobacterium bovisBacillus Calmette Guérin on In Vitro Induction of CD1 Molecules in Human Adherent Mononuclear Cells

Bacillus Calmette-Guerin Down-Regulates CD1b Induction by Granulocyte-Macrophage Colony Stimulating Factor in Human Peripheral Blood Monocytes

BCG-infected adherent mononuclear cells release cytokines that regulate group 1 CD1 molecule expression

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