Abstract
Recent findings established that primary targets of HIV/SIV are lymphoid cells within the gastrointestinal (GI) tract. Focus has therefore shifted to T-cells expressing alpha(4)beta(7) integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of alpha(4)beta(7)+ T-cells in HIV/SIV pathogenesis include their depletion or blockade of their synthesis, binding and/or homing capabilities in vivo. Such studies can ideally be conducted in rhesus macaques (RM), the non-human primate model of AIDS. Characterization of alpha(4)beta(7) expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naïve and TEM (effector memory) T-cells. High densities were observed on TCM (central memory) T-cells. Intravenous administration of a single 50mg/kg dose of recombinant rhesus alpha(4)beta(7) antibody resulted in significant initial decline of alpha(4)beta(7)+ lymphocytes and sustained coating of the alpha(4)beta(7) receptor in both the periphery and GI tissues.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / blood
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Antibodies, Monoclonal / immunology*
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Antibodies, Monoclonal / pharmacology*
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / virology
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Cross-Sectional Studies
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Flow Cytometry
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Gastrointestinal Tract / drug effects
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Gastrointestinal Tract / immunology
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Gastrointestinal Tract / virology
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Integrins / biosynthesis
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Integrins / immunology*
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Longitudinal Studies
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Macaca mulatta
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Male
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Pilot Projects
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RNA, Viral / chemistry
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RNA, Viral / genetics
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Recombinant Proteins / blood
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Recombinant Proteins / immunology
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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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 / genetics
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Simian Immunodeficiency Virus / immunology*
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / virology
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Tretinoin / pharmacology
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Viral Load
Substances
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Antibodies, Monoclonal
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Integrins
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RNA, Viral
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Recombinant Proteins
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integrin alpha4beta7
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Tretinoin