PLoS pathogens, 2013-07, Vol.9 (7), p.e1003471
2013
Details
- Autor(en) / Beteiligte
- Titel
- Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21
- Ist Teil von
- PLoS pathogens, 2013-07, Vol.9 (7), p.e1003471
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs), preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL)-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIV(mac239) and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i) higher expression of perforin and granzyme B in total and SIV-specific CD8⁺ T cells and (ii) higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1003471Titel-ID: cdi_plos_journals_1430782750
- Format
- –
- Schlagworte
- Acquired immune deficiency syndrome, AIDS, Animals, Antiretroviral drugs, Bacterial Translocation - drug effects, Biology, CD8-Positive T-Lymphocytes - drug effects, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, Cell Differentiation - drug effects, Down-Regulation - drug effects, Drug therapy, Female, Genetic aspects, Granzymes - biosynthesis, Granzymes - genetics, Granzymes - metabolism, Health aspects, HIV, HIV (Viruses), Host-parasite relationships, Human immunodeficiency virus, Immune system, Immunity, Mucosal - drug effects, Immunoglobulin Fc Fragments - adverse effects, Immunoglobulin Fc Fragments - genetics, Immunoglobulin Fc Fragments - therapeutic use, Interleukins, Interleukins - adverse effects, Interleukins - genetics, Interleukins - therapeutic use, Intestinal Mucosa - drug effects, Intestinal Mucosa - immunology, Intestinal Mucosa - pathology, Intestinal Mucosa - virology, Macaca mulatta, Medicine, Perforin - biosynthesis, Perforin - genetics, Perforin - metabolism, Physiological aspects, Random Allocation, Recombinant Fusion Proteins - adverse effects, Recombinant Fusion Proteins - genetics, Recombinant Fusion Proteins - therapeutic use, Rhesus monkey, Simian Acquired Immunodeficiency Syndrome - drug therapy, Simian Acquired Immunodeficiency Syndrome - immunology, Simian Acquired Immunodeficiency Syndrome - metabolism, Simian Acquired Immunodeficiency Syndrome - virology, Simian immunodeficiency virus, Simian Immunodeficiency Virus - drug effects, Simian Immunodeficiency Virus - isolation & purification, Simian Immunodeficiency Virus - physiology, Th17 Cells - drug effects, Th17 Cells - immunology, Th17 Cells - pathology, Th17 Cells - virology, Translocation (Genetics), Up-Regulation - drug effects, Viral Load - drug effects