Abstract
Intravenous administration of a novel recombinant rhesus mAb against the α4β7 gut-homing integrin (mAb) into rhesus macaques just prior to and during acute SIV infection resulted in significant decrease in plasma and gastrointestinal (GI) tissue viral load and a marked reduction in GI tissue proviral DNA load as compared with control SIV-infected rhesus macaques. This mAb administration was associated with increases in peripheral blood naive and central memory CD4(+) T cells and maintenance of a high frequency of CCR5(+)CD4(+) T cells. Additionally, such mAb administration inhibited the mobilization of NK cells and plasmacytoid dendritic cells characteristically seen in the control animals during acute infection accompanied by the inhibition of the synthesis of MIP-3α by the gut tissues. These data in concert suggest that blocking of GI trafficking CD4(+) T cells and inhibiting the mobilization of cell lineages of the innate immune system may be a powerful new tool to protect GI tissues and modulate acute lentiviral infection.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acute Disease
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Animals
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Antibodies, Blocking / administration & dosage*
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DNA, Viral / antagonists & inhibitors
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DNA, Viral / blood
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Gastric Mucosa / immunology*
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Gastric Mucosa / metabolism
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Gastric Mucosa / virology
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Injections, Intravenous
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Integrin alpha4 / blood
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Integrin alpha4 / immunology
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Integrin beta Chains / blood
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Integrin beta Chains / immunology
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Integrins / antagonists & inhibitors*
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Integrins / blood
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Integrins / immunology
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / virology
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Macaca mulatta
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Protein Transport / immunology
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Proviruses / genetics
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Proviruses / immunology
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Simian Acquired Immunodeficiency Syndrome / blood
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Simian Acquired Immunodeficiency Syndrome / immunology*
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Simian Acquired Immunodeficiency Syndrome / virology
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Simian Immunodeficiency Virus / immunology*
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Vaccines, Synthetic / administration & dosage
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Viral Load / immunology*
Substances
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Antibodies, Blocking
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DNA, Viral
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Integrin beta Chains
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Integrins
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Vaccines, Synthetic
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integrin alpha4beta7
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integrin beta7
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Integrin alpha4