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 language | English (US) |
|---|---|
| Article number | 136ra69 |
| Journal | Science Translational Medicine |
| Volume | 4 |
| Issue number | 136 |
| DOIs | |
| State | Published - May 30 2012 |
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ASJC Scopus subject areas
- Medicine(all)
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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 journal › Article
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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.
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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 -