Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections

Jason M. Brenchley, Mirko Paiardini, Kenneth S. Knox, Ava I. Asher, Barbara Cervasi, Tedi E. Asher, Phillip Scheinberg, David A. Price, Chadi Hage, Lisa M. Kholi, Alexander Khoruts, Ian Frank, James Else, Timothy Schacker, Guido Silvestri, Daniel C. Douek

Research output: Contribution to journalArticle

443 Citations (Scopus)

Abstract

Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, Gl tract, and broncheoalveolar lavage of HIV-infected and uninfected humans, and SIV-infected and uninfected sooty mangabeys. We found that (1) human Th17 cells are specific for extracellular bacterial and fungal antigens, but not common viral antigens; (2)Th17 cells are infected by HIV in vivo, but not preferentially so; (3) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a Th1 phenotype with cellular maturation; (4) there is significant loss of Th17 cells in the Gl tract of HIV-infected patients; (5) Th17 cells are not preferentially lost from the broncheoalveolar lavage of HIV-infected patients; and (6) SIV-infected sooty mangabeys maintain healthy frequencies of Th17 cells in the blood and Gl tract. These observations further elucidate the immunodeficiency of HIV disease and may provide a mechanistic basis for the mucosal barrier breakdown that characterizes HIV infection. Finally, these data may help account for the nonprogressive nature of nonpathogenic SIV infection in sooty mangabeys.

Original languageEnglish
Pages (from-to)2826-2835
Number of pages10
JournalBlood
Volume112
Issue number7
DOIs
StatePublished - Oct 1 2008

Fingerprint

Th17 Cells
T-cells
Blood
Cercocebus atys
T-Lymphocytes
HIV
Fungal Antigens
Infection
Bacterial Antigens
Viral Antigens
Therapeutic Irrigation
HIV Infections
Phenotype
Gastrointestinal Tract

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Brenchley, J. M., Paiardini, M., Knox, K. S., Asher, A. I., Cervasi, B., Asher, T. E., ... Douek, D. C. (2008). Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood, 112(7), 2826-2835. https://doi.org/10.1182/blood-2008-05-159301

Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. / Brenchley, Jason M.; Paiardini, Mirko; Knox, Kenneth S.; Asher, Ava I.; Cervasi, Barbara; Asher, Tedi E.; Scheinberg, Phillip; Price, David A.; Hage, Chadi; Kholi, Lisa M.; Khoruts, Alexander; Frank, Ian; Else, James; Schacker, Timothy; Silvestri, Guido; Douek, Daniel C.

In: Blood, Vol. 112, No. 7, 01.10.2008, p. 2826-2835.

Research output: Contribution to journalArticle

Brenchley, JM, Paiardini, M, Knox, KS, Asher, AI, Cervasi, B, Asher, TE, Scheinberg, P, Price, DA, Hage, C, Kholi, LM, Khoruts, A, Frank, I, Else, J, Schacker, T, Silvestri, G & Douek, DC 2008, 'Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections', Blood, vol. 112, no. 7, pp. 2826-2835. https://doi.org/10.1182/blood-2008-05-159301
Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008 Oct 1;112(7):2826-2835. https://doi.org/10.1182/blood-2008-05-159301
Brenchley, Jason M. ; Paiardini, Mirko ; Knox, Kenneth S. ; Asher, Ava I. ; Cervasi, Barbara ; Asher, Tedi E. ; Scheinberg, Phillip ; Price, David A. ; Hage, Chadi ; Kholi, Lisa M. ; Khoruts, Alexander ; Frank, Ian ; Else, James ; Schacker, Timothy ; Silvestri, Guido ; Douek, Daniel C. / Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. In: Blood. 2008 ; Vol. 112, No. 7. pp. 2826-2835.
@article{6edc461ba62340768e341a4df8df0dff,
title = "Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections",
abstract = "Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, Gl tract, and broncheoalveolar lavage of HIV-infected and uninfected humans, and SIV-infected and uninfected sooty mangabeys. We found that (1) human Th17 cells are specific for extracellular bacterial and fungal antigens, but not common viral antigens; (2)Th17 cells are infected by HIV in vivo, but not preferentially so; (3) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a Th1 phenotype with cellular maturation; (4) there is significant loss of Th17 cells in the Gl tract of HIV-infected patients; (5) Th17 cells are not preferentially lost from the broncheoalveolar lavage of HIV-infected patients; and (6) SIV-infected sooty mangabeys maintain healthy frequencies of Th17 cells in the blood and Gl tract. These observations further elucidate the immunodeficiency of HIV disease and may provide a mechanistic basis for the mucosal barrier breakdown that characterizes HIV infection. Finally, these data may help account for the nonprogressive nature of nonpathogenic SIV infection in sooty mangabeys.",
author = "Brenchley, {Jason M.} and Mirko Paiardini and Knox, {Kenneth S.} and Asher, {Ava I.} and Barbara Cervasi and Asher, {Tedi E.} and Phillip Scheinberg and Price, {David A.} and Chadi Hage and Kholi, {Lisa M.} and Alexander Khoruts and Ian Frank and James Else and Timothy Schacker and Guido Silvestri and Douek, {Daniel C.}",
year = "2008",
month = "10",
day = "1",
doi = "10.1182/blood-2008-05-159301",
language = "English",
volume = "112",
pages = "2826--2835",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

TY - JOUR

T1 - Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections

AU - Brenchley, Jason M.

AU - Paiardini, Mirko

AU - Knox, Kenneth S.

AU - Asher, Ava I.

AU - Cervasi, Barbara

AU - Asher, Tedi E.

AU - Scheinberg, Phillip

AU - Price, David A.

AU - Hage, Chadi

AU - Kholi, Lisa M.

AU - Khoruts, Alexander

AU - Frank, Ian

AU - Else, James

AU - Schacker, Timothy

AU - Silvestri, Guido

AU - Douek, Daniel C.

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, Gl tract, and broncheoalveolar lavage of HIV-infected and uninfected humans, and SIV-infected and uninfected sooty mangabeys. We found that (1) human Th17 cells are specific for extracellular bacterial and fungal antigens, but not common viral antigens; (2)Th17 cells are infected by HIV in vivo, but not preferentially so; (3) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a Th1 phenotype with cellular maturation; (4) there is significant loss of Th17 cells in the Gl tract of HIV-infected patients; (5) Th17 cells are not preferentially lost from the broncheoalveolar lavage of HIV-infected patients; and (6) SIV-infected sooty mangabeys maintain healthy frequencies of Th17 cells in the blood and Gl tract. These observations further elucidate the immunodeficiency of HIV disease and may provide a mechanistic basis for the mucosal barrier breakdown that characterizes HIV infection. Finally, these data may help account for the nonprogressive nature of nonpathogenic SIV infection in sooty mangabeys.

AB - Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, Gl tract, and broncheoalveolar lavage of HIV-infected and uninfected humans, and SIV-infected and uninfected sooty mangabeys. We found that (1) human Th17 cells are specific for extracellular bacterial and fungal antigens, but not common viral antigens; (2)Th17 cells are infected by HIV in vivo, but not preferentially so; (3) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a Th1 phenotype with cellular maturation; (4) there is significant loss of Th17 cells in the Gl tract of HIV-infected patients; (5) Th17 cells are not preferentially lost from the broncheoalveolar lavage of HIV-infected patients; and (6) SIV-infected sooty mangabeys maintain healthy frequencies of Th17 cells in the blood and Gl tract. These observations further elucidate the immunodeficiency of HIV disease and may provide a mechanistic basis for the mucosal barrier breakdown that characterizes HIV infection. Finally, these data may help account for the nonprogressive nature of nonpathogenic SIV infection in sooty mangabeys.

UR - http://www.scopus.com/inward/record.url?scp=53449093632&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53449093632&partnerID=8YFLogxK

U2 - 10.1182/blood-2008-05-159301

DO - 10.1182/blood-2008-05-159301

M3 - Article

C2 - 18664624

AN - SCOPUS:53449093632

VL - 112

SP - 2826

EP - 2835

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -