Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques

Luca Micci, Barbara Cervasi, Zachary S. Ende, Robin I. Iriele, Elane Reyes-Aviles, Carol Vinton, James Else, Guido Silvestri, Aftab A. Ansari, Francois Villinger, Savita G Pahwa, Jacob D. Estes, Jason M. Brenchley, Mirko Paiardini

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3925-3935
Number of pages11
JournalBlood
Volume120
Issue number19
DOIs
StatePublished - Nov 8 2012

Fingerprint

Th17 Cells
T-cells
Macaca mulatta
T-Lymphocytes
Infection
Cercocebus atys
Blood
interleukin-21
Data storage equipment
Antibody-Producing Cells
Interleukin-17
Plasma Cells
Primates
HIV Infections
Disease Progression
Mucous Membrane
Homeostasis
B-Lymphocytes
Cells
Maintenance

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Micci, L., Cervasi, B., Ende, Z. S., Iriele, R. I., Reyes-Aviles, E., Vinton, C., ... Paiardini, M. (2012). Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques. Blood, 120(19), 3925-3935. https://doi.org/10.1182/blood-2012-04-420240

Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques. / Micci, Luca; Cervasi, Barbara; Ende, Zachary S.; Iriele, Robin I.; Reyes-Aviles, Elane; Vinton, Carol; Else, James; Silvestri, Guido; Ansari, Aftab A.; Villinger, Francois; Pahwa, Savita G; Estes, Jacob D.; Brenchley, Jason M.; Paiardini, Mirko.

In: Blood, Vol. 120, No. 19, 08.11.2012, p. 3925-3935.

Research output: Contribution to journalArticle

Micci, L, Cervasi, B, Ende, ZS, Iriele, RI, Reyes-Aviles, E, Vinton, C, Else, J, Silvestri, G, Ansari, AA, Villinger, F, Pahwa, SG, Estes, JD, Brenchley, JM & Paiardini, M 2012, 'Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques', Blood, vol. 120, no. 19, pp. 3925-3935. https://doi.org/10.1182/blood-2012-04-420240
Micci, Luca ; Cervasi, Barbara ; Ende, Zachary S. ; Iriele, Robin I. ; Reyes-Aviles, Elane ; Vinton, Carol ; Else, James ; Silvestri, Guido ; Ansari, Aftab A. ; Villinger, Francois ; Pahwa, Savita G ; Estes, Jacob D. ; Brenchley, Jason M. ; Paiardini, Mirko. / Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques. In: Blood. 2012 ; Vol. 120, No. 19. pp. 3925-3935.
@article{9b14ff796e074bf5a139a745eb3c24a4,
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.",
author = "Luca Micci and Barbara Cervasi and Ende, {Zachary S.} and Iriele, {Robin I.} and Elane Reyes-Aviles and Carol Vinton and James Else and Guido Silvestri and Ansari, {Aftab A.} and Francois Villinger and Pahwa, {Savita G} and Estes, {Jacob D.} and Brenchley, {Jason M.} and Mirko Paiardini",
year = "2012",
month = "11",
day = "8",
doi = "10.1182/blood-2012-04-420240",
language = "English",
volume = "120",
pages = "3925--3935",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "19",

}

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 G

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.

UR - http://www.scopus.com/inward/record.url?scp=84868609542&partnerID=8YFLogxK

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

VL - 120

SP - 3925

EP - 3935

JO - Blood

JF - Blood

SN - 0006-4971

IS - 19

ER -