Details

Autor(en) / Beteiligte

• Pallikkuth, Suresh
• Micci, Luca
• Ende, Zachary S
• Iriele, Robin I
• Cervasi, Barbara
• Lawson, Benton
• McGary, Colleen S
• Rogers, Kenneth A
• Else, James G
• Silvestri, Guido
• Easley, Kirk
• Estes, Jacob D
• Villinger, Francois
• Pahwa, Savita
• Paiardini, Mirko

Titel

Maintenance of Intestinal Th17 Cells and Reduced Microbial Translocation in SIV-infected Rhesus Macaques Treated with Interleukin (IL)-21: e1003471

Ist Teil von

• PLoS pathogens, 2013-07, Vol.9 (7)

Ort / Verlag

San Francisco: Public Library of Science

Erscheinungsjahr

2013

Link zum Volltext

Quelle

EZB Free E-Journals

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 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.