PLoS pathogens, 2018-02, Vol.14 (2), p.e1006902-e1006902
2018
Details
- Autor(en) / Beteiligte
- Titel
- Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes
- Ist Teil von
- PLoS pathogens, 2018-02, Vol.14 (2), p.e1006902-e1006902
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. ClinicalTrials.gov NCT02452268.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1006902Titel-ID: cdi_plos_journals_2014518564
- Format
- –
- Schlagworte
- Acquired immune deficiency syndrome, Adjuvants, Immunologic - therapeutic use, AIDS, Animals, B-Lymphocytes - drug effects, B-Lymphocytes - pathology, Biology and life sciences, Biomedical research, Cancer, CD8 antigen, CD8-Positive T-Lymphocytes - drug effects, CD8-Positive T-Lymphocytes - pathology, Chronic infection, Cytokines, Cytometry, Cytotoxicity, Female, Follicles, Funding, Genetic aspects, Germinal Center - drug effects, Germinal Center - pathology, Granzyme B, Health aspects, HIV, HIV (Viruses), Human immunodeficiency virus, Image analysis, Image processing, Immune privilege, Immunotherapy, Immunotherapy - methods, Infections, Infectious diseases, Interleukin 15, Interleukin-15 - chemistry, Interleukin-15 - metabolism, Interleukin-15 - therapeutic use, Interleukins, Laboratories, Lymph nodes, Lymph Nodes - metabolism, Lymph Nodes - pathology, Lymph Nodes - virology, Lymphatic system, Lymphocyte Count, Lymphocytes, Lymphocytes B, Lymphocytes T, Lymphoid tissue, Macaca mulatta, Major histocompatibility complex, Male, Medical research, Medicine and Health Sciences, Methods, Mucosa, Pathogenesis, Protein Multimerization, Research and Analysis Methods, Ribonucleic acid, RNA, RNA sequencing, RNA, Viral - analysis, RNA, Viral - metabolism, Sanctuaries, Simian Acquired Immunodeficiency Syndrome - drug therapy, Simian Acquired Immunodeficiency Syndrome - immunology, Simian Acquired Immunodeficiency Syndrome - virology, Simian Immunodeficiency Virus - genetics, Simian Immunodeficiency Virus - metabolism, Supervision, T-Lymphocytes, Cytotoxic - drug effects, T-Lymphocytes, Cytotoxic - pathology, T-Lymphocytes, Helper-Inducer - drug effects, T-Lymphocytes, Helper-Inducer - pathology, Tissues, Viral infections, Viremia, Viruses