|Title||Paucity of interleukin (IL-21)-producing CD4+ T-cells is associated with Th17 cell depletion in SIV-infection of rhesus macaques.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Micci L, Cervasi B, Ende ZS, Iriele RI, Reyes-Aviles E, Vinton C, Else JG, Silvestri G, Ansari AA, Villinger F, Pahwa S, Estes JD, Brenchley JM, Paiardini M|
|Date Published||2012 Sep 18|
Interleukin (IL)-21 regulates Th17 cell homeostasis, enhances the differentiation of memory B cells and antibody-secreting plasma cells, and promotes the maintenance of CD8(+) T-cell responses. In this study, we investigated the phenotype, function, and frequency of blood and intestinal IL-21-producing cells in nonhuman primates that are hosts of progressive (rhesus macaques; RMs) and nonprogressive (sooty mangabeys; SMs) SIV infection. We found that, in both species, memory CD4(+)CD95(+)CCR6(-) T-cells are the main IL-21 producers, and that only a small fraction of CD4(+)IL-21(+) T-cells produce IL-17. During chronic SIV infection of RMs, CD4(+)IL-21(+) T-cells were significantly depleted in both blood and rectal mucosa, with the extent of this depletion correlating with the loss of Th17 cells. Furthermore, treatment with IL-21 increased the in vivo levels of Th17 cells in SIV-infected RMs. In contrast, normal levels of CD4(+)IL-21(+) T-cells were found in SIV-infected SMs. Collectively, these data indicate that depletion of IL-21-producing CD4(+) T-cells distinguishes progressive from nonprogressive SIV infection of RMs and SMs, and suggest that depletion of CD4(+)IL-21(+) T-cells is involved in the preferential loss of Th17 cells that is associated with SIV disease progression. Further pre-clinical studies of IL-21 as a potential immunotherapeutic agent for HIV infection may be warranted.