TY - JOUR
T1 - Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques
AU - Micci, Luca
AU - Cervasi, Barbara
AU - Ende, Zachary S.
AU - Iriele, Robin I.
AU - Reyes-Aviles, Elane
AU - Vinton, Carol
AU - Else, James
AU - Silvestri, Guido
AU - Ansari, Aftab A.
AU - Villinger, Francois
AU - Pahwa, Savita
AU - Estes, Jacob D.
AU - Brenchley, Jason M.
AU - Paiardini, Mirko
PY - 2012/11/8
Y1 - 2012/11/8
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84868609542&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-04-420240
DO - 10.1182/blood-2012-04-420240
M3 - Article
C2 - 22990011
AN - SCOPUS:84868609542
SN - 0006-4971
VL - 120
SP - 3925
EP - 3935
JO - Blood
JF - Blood
IS - 19
ER -