title: Paucity of IL-21-producing CD4(+) T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques.
abstract: 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 preclinical studies of IL-21 as a potential immunotherapeutic agent for HIV infection may be warranted.
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Micci
authors.forename: Barbara
authors.initials: B
authors.lastname: Cervasi
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Ende
authors.forename: Robin I
authors.initials: RI
authors.lastname: Iriele
authors.forename: Elane
authors.initials: E
authors.lastname: Reyes-Aviles
authors.forename: Carol
authors.initials: C
authors.lastname: Vinton
authors.forename: James
authors.initials: J
authors.lastname: Else
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology; D016130:Immunophenotyping; D007378:Interleukins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D010641:Phenotype; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D000098546:Interleukin-21