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Maintenance of Intestinal Th17 Cells and Reduced Microbial Translocation in SIV-infected Rhesus Macaques Treated with Interleukin (IL)-21
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نویسنده
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pallikkuth s. ,micci l. ,ende z.s. ,iriele r.i. ,cervasi b. ,lawson b. ,mcgary c.s. ,rogers k.a. ,else j.g. ,silvestri g. ,easley k. ,estes j.d. ,villinger f. ,pahwa s. ,paiardini m.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 7
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چکیده
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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 sivmac239 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.
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آدرس
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university of miami miller school of medicine,miami,fl, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga,united states,department of pathology and laboratory medicine,emory university,atlanta,ga, United States, department of biostatistics and bioinformatics,rollins school of public health,atlanta,ga, United States, aids and cancer virus program,frederick national laboratory for cancer research,saic-frederick,frederick,md, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga, United States, university of miami miller school of medicine,miami,fl, United States, division of microbiology and immunology,yerkes national primate research center,emory university,atlanta,ga,united states,department of pathology and laboratory medicine,emory university,atlanta,ga, United States
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Authors
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