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PLoS Pathog ; 14(2): e1006902, 2018 02.
Article in English | MEDLINE | ID: mdl-29474450

ABSTRACT

B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN. Following hetIL-15 treatment, multiplexed quantitative image analysis (histo-cytometry) of LN revealed increased numbers of granzyme B+ T cells in B cell follicles and SHIV RNA was decreased in plasma and in LN. Based on these properties, hetIL-15 shows promise as a potential component in combination immunotherapy regimens to target AIDS virus sanctuaries and reduce long-term viral reservoirs in HIV-1 infected individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT02452268.


Subject(s)
Interleukin-15/therapeutic use , Lymph Nodes/metabolism , RNA, Viral/metabolism , Simian Acquired Immunodeficiency Syndrome/drug therapy , Simian Immunodeficiency Virus/genetics , T-Lymphocytes, Cytotoxic/drug effects , Adjuvants, Immunologic/therapeutic use , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/pathology , Female , Germinal Center/drug effects , Germinal Center/pathology , Immunotherapy/methods , Interleukin-15/chemistry , Interleukin-15/metabolism , Lymph Nodes/pathology , Lymph Nodes/virology , Lymphocyte Count , Macaca mulatta , Male , Protein Multimerization , RNA, Viral/analysis , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/metabolism , T-Lymphocytes, Cytotoxic/pathology , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Helper-Inducer/pathology
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