Regulation of parasite antigen-driven immune responses by interleukin-10 (IL-10) and IL-12 in lymphatic filariasis.
Identifieur interne : 005014 ( PubMed/Corpus ); précédent : 005013; suivant : 005015Regulation of parasite antigen-driven immune responses by interleukin-10 (IL-10) and IL-12 in lymphatic filariasis.
Auteurs : S. Mahanty ; M. Ravichandran ; U. Raman ; K. Jayaraman ; V. Kumaraswami ; T B NutmanSource :
- Infection and immunity [ 0019-9567 ] ; 1997.
English descriptors
- KwdEn :
- Adolescent, Adult, Animals, Antibodies, Blocking (immunology), Antibodies, Monoclonal (immunology), Antigens, Helminth (immunology), Brugia malayi (immunology), Cell Division, Down-Regulation, Elephantiasis, Filarial (immunology), Enzyme-Linked Immunosorbent Assay, Female, Humans, Interferon-gamma (biosynthesis), Interleukin-10 (immunology), Interleukin-12 (genetics), Interleukin-12 (immunology), Interleukin-5 (immunology), Leukocytes, Mononuclear (immunology), Male, Middle Aged, Neutralization Tests, Recombinant Proteins (immunology), T-Lymphocytes (cytology), T-Lymphocytes (immunology), Th1 Cells (immunology), Th2 Cells (immunology), Tuberculin (immunology).
- MESH :
- chemical , biosynthesis : Interferon-gamma.
- chemical , genetics : Interleukin-12.
- chemical , immunology : Antibodies, Blocking, Antibodies, Monoclonal, Antigens, Helminth, Interleukin-10, Interleukin-12, Interleukin-5, Recombinant Proteins, Tuberculin.
- cytology : T-Lymphocytes.
- immunology : Brugia malayi, Elephantiasis, Filarial, Leukocytes, Mononuclear, T-Lymphocytes, Th1 Cells, Th2 Cells.
- Adolescent, Adult, Animals, Cell Division, Down-Regulation, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Neutralization Tests.
Abstract
We investigated the mechanisms by which interleukin-10 (IL-10) regulates antigen-specific hyporesponsiveness in asymptomatic microfilaremic (MF) individuals. Peripheral blood mononuclear cells from MF individuals (n = 11) were stimulated in vitro with Brugia malayi antigen (BMA) or mycobacterial purified protein derivative (PPD) in the presence of neutralizing anti-IL-10 or isotype control monoclonal antibodies. As expected, BMA stimulated little or no gamma interferon (IFN-gamma) secretion in MF individuals, whereas PPD stimulated IFN-gamma in all but one. Neutralization of endogenous BMA-driven IL-10 secretion led to augmentation of IFN-gamma in seven of nine MF individuals (1.5- to 10-fold) and did so in a BMA-specific manner (PPD-driven IFN-gamma was augmented in only two of eight MF individuals and only 1.5- to 2-fold), indicating that IL-10 downregulates type 1 responses in these individuals. Type 2 responses (IL-5 secretion) were unaffected by the IL-10 blockade. To assess whether IL-12 could reverse the type 1 downregulation observed, the effect of recombinant human IL-12 (rhIL-12) on BMA-driven IL-5 and IFN-gamma production was also evaluated. rhIL-12 augmented both BMA- and PPD-driven IFN-gamma production 5- to 10-fold in six of nine MF individuals. These data demonstrate that IL-10 downregulates BMA-driven type 1 responses and that IL-12 can overcome downregulation of Th1 responses associated with MF but does so in a non-antigen-specific manner.
PubMed: 9125556
Links to Exploration step
pubmed:9125556Le document en format XML
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<front><div type="abstract" xml:lang="en">We investigated the mechanisms by which interleukin-10 (IL-10) regulates antigen-specific hyporesponsiveness in asymptomatic microfilaremic (MF) individuals. Peripheral blood mononuclear cells from MF individuals (n = 11) were stimulated in vitro with Brugia malayi antigen (BMA) or mycobacterial purified protein derivative (PPD) in the presence of neutralizing anti-IL-10 or isotype control monoclonal antibodies. As expected, BMA stimulated little or no gamma interferon (IFN-gamma) secretion in MF individuals, whereas PPD stimulated IFN-gamma in all but one. Neutralization of endogenous BMA-driven IL-10 secretion led to augmentation of IFN-gamma in seven of nine MF individuals (1.5- to 10-fold) and did so in a BMA-specific manner (PPD-driven IFN-gamma was augmented in only two of eight MF individuals and only 1.5- to 2-fold), indicating that IL-10 downregulates type 1 responses in these individuals. Type 2 responses (IL-5 secretion) were unaffected by the IL-10 blockade. To assess whether IL-12 could reverse the type 1 downregulation observed, the effect of recombinant human IL-12 (rhIL-12) on BMA-driven IL-5 and IFN-gamma production was also evaluated. rhIL-12 augmented both BMA- and PPD-driven IFN-gamma production 5- to 10-fold in six of nine MF individuals. These data demonstrate that IL-10 downregulates BMA-driven type 1 responses and that IL-12 can overcome downregulation of Th1 responses associated with MF but does so in a non-antigen-specific manner.</div>
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<Abstract><AbstractText>We investigated the mechanisms by which interleukin-10 (IL-10) regulates antigen-specific hyporesponsiveness in asymptomatic microfilaremic (MF) individuals. Peripheral blood mononuclear cells from MF individuals (n = 11) were stimulated in vitro with Brugia malayi antigen (BMA) or mycobacterial purified protein derivative (PPD) in the presence of neutralizing anti-IL-10 or isotype control monoclonal antibodies. As expected, BMA stimulated little or no gamma interferon (IFN-gamma) secretion in MF individuals, whereas PPD stimulated IFN-gamma in all but one. Neutralization of endogenous BMA-driven IL-10 secretion led to augmentation of IFN-gamma in seven of nine MF individuals (1.5- to 10-fold) and did so in a BMA-specific manner (PPD-driven IFN-gamma was augmented in only two of eight MF individuals and only 1.5- to 2-fold), indicating that IL-10 downregulates type 1 responses in these individuals. Type 2 responses (IL-5 secretion) were unaffected by the IL-10 blockade. To assess whether IL-12 could reverse the type 1 downregulation observed, the effect of recombinant human IL-12 (rhIL-12) on BMA-driven IL-5 and IFN-gamma production was also evaluated. rhIL-12 augmented both BMA- and PPD-driven IFN-gamma production 5- to 10-fold in six of nine MF individuals. These data demonstrate that IL-10 downregulates BMA-driven type 1 responses and that IL-12 can overcome downregulation of Th1 responses associated with MF but does so in a non-antigen-specific manner.</AbstractText>
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