SIV replication in the infected rhesus macaque is limited by the size of the preexisting T H17 cell compartment

Dennis Hartigan-O'Connor, Kristina Abel, Koen K A Van Rompay, Bittoo Kanwar, Joseph M. McCune

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The mechanisms by which some HIV-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. Viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. However, it has been difficult to identify host immune functions that may be present before infection and that allow resistance to lentiviral disease progression. Here, we show that simian immunodeficiency virus replication in the infected rhesus macaque is limited by the size of the preexisting T helper 17 (T H17) cell compartment: Animals with a high representation of such cells in blood and intestinal tissue before infection experienced peak and set-point viral loads about one log unit lower than those with a lower representation of T H17 cells. Reciprocally, treatment of macaques with interleukin-2 and granulocyte colony-stimulating factor before infection led to depletion of T H17 cells, reduction of the ratio between T H17 cells and CD3 +CD4 +CD25 +CD127 low regulatory T cells, and higher viral loads for 6 months after infection. These results demonstrate that the composition of the host immune system before infection has an influence on the course of disease after infection. Furthermore, to the extent that this influence shapes and interacts with T cell-mediated responses to virus, our findings provide a new framework for understanding interindividual variation in responses to therapies and vaccines against HIV.

Original languageEnglish (US)
Article number136ra69
JournalScience Translational Medicine
Volume4
Issue number136
DOIs
StatePublished - May 30 2012

Fingerprint

Th17 Cells
Macaca mulatta
Infection
Viral Load
Disease Progression
Active Immunotherapy
AIDS Vaccines
Simian Immunodeficiency Virus
Macaca
Granulocyte Colony-Stimulating Factor
Regulatory T-Lymphocytes
Virus Replication
Major Histocompatibility Complex
Interleukin-2
Immune System
Blood Cells
Alleles
HIV
Viruses
T-Lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

SIV replication in the infected rhesus macaque is limited by the size of the preexisting T H17 cell compartment. / Hartigan-O'Connor, Dennis; Abel, Kristina; Van Rompay, Koen K A; Kanwar, Bittoo; McCune, Joseph M.

In: Science Translational Medicine, Vol. 4, No. 136, 136ra69, 30.05.2012.

Research output: Contribution to journalArticle

Hartigan-O'Connor, Dennis ; Abel, Kristina ; Van Rompay, Koen K A ; Kanwar, Bittoo ; McCune, Joseph M. / SIV replication in the infected rhesus macaque is limited by the size of the preexisting T H17 cell compartment. In: Science Translational Medicine. 2012 ; Vol. 4, No. 136.
@article{1f81f26416154b99a3abcdcbe61784e4,
title = "SIV replication in the infected rhesus macaque is limited by the size of the preexisting T H17 cell compartment",
abstract = "The mechanisms by which some HIV-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. Viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. However, it has been difficult to identify host immune functions that may be present before infection and that allow resistance to lentiviral disease progression. Here, we show that simian immunodeficiency virus replication in the infected rhesus macaque is limited by the size of the preexisting T helper 17 (T H17) cell compartment: Animals with a high representation of such cells in blood and intestinal tissue before infection experienced peak and set-point viral loads about one log unit lower than those with a lower representation of T H17 cells. Reciprocally, treatment of macaques with interleukin-2 and granulocyte colony-stimulating factor before infection led to depletion of T H17 cells, reduction of the ratio between T H17 cells and CD3 +CD4 +CD25 +CD127 low regulatory T cells, and higher viral loads for 6 months after infection. These results demonstrate that the composition of the host immune system before infection has an influence on the course of disease after infection. Furthermore, to the extent that this influence shapes and interacts with T cell-mediated responses to virus, our findings provide a new framework for understanding interindividual variation in responses to therapies and vaccines against HIV.",
author = "Dennis Hartigan-O'Connor and Kristina Abel and {Van Rompay}, {Koen K A} and Bittoo Kanwar and McCune, {Joseph M.}",
year = "2012",
month = "5",
day = "30",
doi = "10.1126/scitranslmed.3003941",
language = "English (US)",
volume = "4",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "136",

}

TY - JOUR

T1 - SIV replication in the infected rhesus macaque is limited by the size of the preexisting T H17 cell compartment

AU - Hartigan-O'Connor, Dennis

AU - Abel, Kristina

AU - Van Rompay, Koen K A

AU - Kanwar, Bittoo

AU - McCune, Joseph M.

PY - 2012/5/30

Y1 - 2012/5/30

N2 - The mechanisms by which some HIV-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. Viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. However, it has been difficult to identify host immune functions that may be present before infection and that allow resistance to lentiviral disease progression. Here, we show that simian immunodeficiency virus replication in the infected rhesus macaque is limited by the size of the preexisting T helper 17 (T H17) cell compartment: Animals with a high representation of such cells in blood and intestinal tissue before infection experienced peak and set-point viral loads about one log unit lower than those with a lower representation of T H17 cells. Reciprocally, treatment of macaques with interleukin-2 and granulocyte colony-stimulating factor before infection led to depletion of T H17 cells, reduction of the ratio between T H17 cells and CD3 +CD4 +CD25 +CD127 low regulatory T cells, and higher viral loads for 6 months after infection. These results demonstrate that the composition of the host immune system before infection has an influence on the course of disease after infection. Furthermore, to the extent that this influence shapes and interacts with T cell-mediated responses to virus, our findings provide a new framework for understanding interindividual variation in responses to therapies and vaccines against HIV.

AB - The mechanisms by which some HIV-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. Viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. However, it has been difficult to identify host immune functions that may be present before infection and that allow resistance to lentiviral disease progression. Here, we show that simian immunodeficiency virus replication in the infected rhesus macaque is limited by the size of the preexisting T helper 17 (T H17) cell compartment: Animals with a high representation of such cells in blood and intestinal tissue before infection experienced peak and set-point viral loads about one log unit lower than those with a lower representation of T H17 cells. Reciprocally, treatment of macaques with interleukin-2 and granulocyte colony-stimulating factor before infection led to depletion of T H17 cells, reduction of the ratio between T H17 cells and CD3 +CD4 +CD25 +CD127 low regulatory T cells, and higher viral loads for 6 months after infection. These results demonstrate that the composition of the host immune system before infection has an influence on the course of disease after infection. Furthermore, to the extent that this influence shapes and interacts with T cell-mediated responses to virus, our findings provide a new framework for understanding interindividual variation in responses to therapies and vaccines against HIV.

UR - http://www.scopus.com/inward/record.url?scp=84861720745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861720745&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.3003941

DO - 10.1126/scitranslmed.3003941

M3 - Article

VL - 4

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 136

M1 - 136ra69

ER -