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

Prete, Salvatore Pasquale; Giuliani, Alessandro; Iona, Elisabetta; Fattorini, Lanfranco; Orefici, Graziella; Franzese, Ornella; Bonmassar, Enzo; Graziani, Grazia

doi:10.1179/joc.2001.13.1.52

Cited by 9 publications

(10 citation statements)

References 21 publications

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“…Preliminary studies performed in our laboratory showed that chemical inactivation of BCG with rifampin does not prevent the inhibitory effect of the microorganism on CD1b expression (28). Therefore, further experiments were carried out using either viable or heat-killed BCG (BCG-H) organisms.…”

Section: Influence Of Bcg On the Induction Of Group I Cd1 Molecules Bmentioning

confidence: 99%

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: Influence Of Bcg On the Induction Of Group I Cd1 Molecules Bmentioning

confidence: 99%

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

et al. 2001

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“…13,47 It has therefore been suggested that the unsatisfactory results in the treatment of tuberculosis obtained with BCG vaccination may be due to mycobacterium-induced impairment of the CD1 system. 48 Similar to the role of CD1 molecule down-regulation in the inefficient immune response toward mycobacteria, we hypothesized that CD1 down-regulation might play a role in escaping the immune system in melanoma, as tumor expressed gangliosides have been shown to be immunogenic but do not elicit a clinically effective immune response. 49 -52 When CD1 expression was analyzed in melanoma lesions, we found significantly higher CD1a, b, c, d expression in primary compared to metastatic lesions in situ (Figures 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

Metastatic Melanoma Secreted IL-10 Down-Regulates CD1 Molecules on Dendritic Cells in Metastatic Tumor Lesions

Gerlini

Tun-Kyi

Dudli

et al. 2004

The American Journal of Pathology

130

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CD1 molecules are expressed by antigen-presenting cells such as dendritic cells and mediate primary immune responses to lipids and glycolipids which have been shown to be expressed by various tumors. Glycolipids are expressed by melanoma cells but, despite their immunogenicity, no efficient spontaneous immune responses are elicited. As IL-10 has previously been shown to down-regulate CD1a on dendritic cells and is known to be expressed by various melanoma cell lines, we investigated if melanoma-derived IL-10 could down-regulate CD1 molecule expression on dendritic cells as a possible way to circumvent immune recognition. We found that CD1a, CD1b, CD1c, and CD1d were significantly down-regulated on dendritic cells in metastatic (n ‫؍‬ 10) but not in primary melanoma lesions (n ‫؍‬ 10). We further detected significantly higher IL-10 protein levels in metastatic than in primary melanomas. Moreover, supernatants from metastatic melanomas were significantly more effective in down-regulating CD1 molecules on dendritic cells than supernatants from primary melanoma cultures. This effect was blocked using a neutralizing IL-10 antibody in a dose dependent manner. Our findings suggest that metastatic but not primary melanomas can down-regulate CD1 molecules on infiltrating dendritic cells by secreting IL-10 which may represent a novel way to escape the immune response directed against the tumor. CD1 molecules are cell surface glycoproteins and represent a non-classical, non-polymorphic antigen-presenting system which is distantly related to major histocompatibility complex (MHC) class I and class II molecules. While MHC molecules form complexes with peptides, the CD1 system presents lipids and glycolipids of self and foreign origin.

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“…Studies performed in our laboratory [18,23] and elsewhere [24] showed that infection of human AMNC with BCG is able to restrain GM-CSF induced upregulation of CD1 molecules. However, we have demonstrated a limited CD1 induction in AMNC following in vitro exposure to BCG alone [18,23].…”

Section: Introductionmentioning

confidence: 98%

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

Cited by 9 publications

References 21 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

Metastatic Melanoma Secreted IL-10 Down-Regulates CD1 Molecules on Dendritic Cells in Metastatic Tumor Lesions

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

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