Abstract
Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8–32 week) ART, depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8+ T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 656-668 |
| Number of pages | 13 |
| Journal | Immunity |
| Volume | 45 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 20 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
Cite this
CD8+ Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy. / Cartwright, Emily K.; Spicer, Lori; Smith, S. Abigail; Lee, David; Fast, Randy; Paganini, Sara; Lawson, Benton O.; Nega, Melon; Easley, Kirk; Schmitz, Joern E.; Bosinger, Steven E.; Paiardini, Mirko; Chahroudi, Ann; Vanderford, Thomas H.; Estes, Jacob; Lifson, Jeffrey D.; Derdeyn, Cynthia A.; Silvestri, Guido.
In: Immunity, Vol. 45, No. 3, 20.09.2016, p. 656-668.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD8+ Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy
AU - Cartwright, Emily K.
AU - Spicer, Lori
AU - Smith, S. Abigail
AU - Lee, David
AU - Fast, Randy
AU - Paganini, Sara
AU - Lawson, Benton O.
AU - Nega, Melon
AU - Easley, Kirk
AU - Schmitz, Joern E.
AU - Bosinger, Steven E.
AU - Paiardini, Mirko
AU - Chahroudi, Ann
AU - Vanderford, Thomas H.
AU - Estes, Jacob
AU - Lifson, Jeffrey D.
AU - Derdeyn, Cynthia A.
AU - Silvestri, Guido
PY - 2016/9/20
Y1 - 2016/9/20
N2 - Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8–32 week) ART, depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8+ T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.
AB - Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8–32 week) ART, depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8+ T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.
UR - http://www.scopus.com/inward/record.url?scp=84990938500&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84990938500&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2016.08.018
DO - 10.1016/j.immuni.2016.08.018
M3 - Article
C2 - 27653601
AN - SCOPUS:84990938500
VL - 45
SP - 656
EP - 668
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -