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Increased soluble IL-7 receptor concentrations associate with improved IL-7 therapy outcomes in SIV-infected ART-treated Rhesus macaques.

Abstract The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven effective in HIV infection, cancer and bone marrow transplantation. Mediating its activity through membrane-bound IL-7 receptor α (mCD127), IL-7 therapy increases T-cell numbers and survival. A soluble form, sCD127, is found in plasma, and we have previously identified increased plasma sCD127 concentrations in HIV infection. Furthermore, patients with high sCD127 exhibited the best viral control, implicating a role for IL-7 or sCD127 directly in improved virologic/immunologic outcomes. The role of the cytokine IL-7 in elevating sCD127 levels was addressed here through assessment of retrospective samples obtained from SIV-infected antiretroviral (ART)-treated Rhesus macaques. IL-7 was administered in clustered weekly doses, allowing for an assessment prior, during and following IL-7 administration. The levels of sCD127 remained relatively unchanged during both early SIV infection and following initiation of ART. However, treatment with IL-7 increased sCD127 concentrations in most animals, transiently or persistently, paralleling increased T-cell numbers, correlating significantly with CD8+ T-cell levels. In addition, proliferating CD4+ or CD8+ T-cells (measured by Ki67) increased in association with elevated sCD127 concentrations. Finally, a high concentration of sCD127 in IL7-treated animals was associated with increased retention of T-cells (measured by BrDU). In addition, a lack, or loss of viral control was associated with more pronounced and frequent elevations in plasma sCD127 concentrations with IL-7 therapy. In summary, plasma sCD127 levels in SIV-infected ART-treated macaques was associated with therapeutic IL-7 administration, with higher sCD127 levels in macaques demonstrating the best T-cell responses. This study furthers our knowledge regarding the interrelationship between increased IL-7 levels and elevated sCD127 levels that may have implications for future IL-7 immunotherapeutic approaches in HIV-infected patients.
PMID
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Keywords
Journal Title plos one
Publication Year Start




 
PMID- 29261677
OWN - NLM
STAT- In-Process
LR  - 20171224
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 12
DP  - 2017
TI  - Increased soluble IL-7 receptor concentrations associate with improved IL-7
      therapy outcomes in SIV-infected ART-treated Rhesus macaques.
PG  - e0188427
LID - 10.1371/journal.pone.0188427 [doi]
AB  - The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven
      effective in HIV infection, cancer and bone marrow transplantation. Mediating its
      activity through membrane-bound IL-7 receptor alpha (mCD127), IL-7 therapy
      increases T-cell numbers and survival. A soluble form, sCD127, is found in
      plasma, and we have previously identified increased plasma sCD127 concentrations 
      in HIV infection. Furthermore, patients with high sCD127 exhibited the best viral
      control, implicating a role for IL-7 or sCD127 directly in improved
      virologic/immunologic outcomes. The role of the cytokine IL-7 in elevating sCD127
      levels was addressed here through assessment of retrospective samples obtained
      from SIV-infected antiretroviral (ART)-treated Rhesus macaques. IL-7 was
      administered in clustered weekly doses, allowing for an assessment prior, during 
      and following IL-7 administration. The levels of sCD127 remained relatively
      unchanged during both early SIV infection and following initiation of ART.
      However, treatment with IL-7 increased sCD127 concentrations in most animals,
      transiently or persistently, paralleling increased T-cell numbers, correlating
      significantly with CD8+ T-cell levels. In addition, proliferating CD4+ or CD8+
      T-cells (measured by Ki67) increased in association with elevated sCD127
      concentrations. Finally, a high concentration of sCD127 in IL7-treated animals
      was associated with increased retention of T-cells (measured by BrDU). In
      addition, a lack, or loss of viral control was associated with more pronounced
      and frequent elevations in plasma sCD127 concentrations with IL-7 therapy. In
      summary, plasma sCD127 levels in SIV-infected ART-treated macaques was associated
      with therapeutic IL-7 administration, with higher sCD127 levels in macaques
      demonstrating the best T-cell responses. This study furthers our knowledge
      regarding the interrelationship between increased IL-7 levels and elevated sCD127
      levels that may have implications for future IL-7 immunotherapeutic approaches in
      HIV-infected patients.
FAU - Steele, Amanda K
AU  - Steele AK
AD  - Center for Infectious Disease Research, Seattle, WA, United States of America.
AD  - Collegiate Peaks Science Writing, Denver, CO, United States of America.
FAU - Carrasco-Medina, Lorna
AU  - Carrasco-Medina L
AD  - The Ottawa Hospital-General Campus, Division of Infectious Diseases, Ottawa, ON, 
      Canada.
FAU - Sodora, Donald L
AU  - Sodora DL
AD  - Center for Infectious Disease Research, Seattle, WA, United States of America.
FAU - Crawley, Angela M
AU  - Crawley AM
AUID- ORCID: http://orcid.org/0000-0002-7453-7922
AD  - The Ottawa Hospital Research Institute, Chronic Disease Program, Ottawa, ON,
      Canada.
AD  - University of Ottawa, Dept. Biochem., Microbiol., and Immunol., Ottawa, ON,
      Canada.
AD  - Carleton University, Dept. Biol., Ottawa, ON, Canada.
LA  - eng
PT  - Journal Article
DEP - 20171219
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
PMC - PMC5736176
EDAT- 2017/12/21 06:00
MHDA- 2017/12/21 06:00
CRDT- 2017/12/21 06:00
PHST- 2017/07/31 00:00 [received]
PHST- 2017/11/07 00:00 [accepted]
PHST- 2017/12/21 06:00 [entrez]
PHST- 2017/12/21 06:00 [pubmed]
PHST- 2017/12/21 06:00 [medline]
AID - 10.1371/journal.pone.0188427 [doi]
AID - PONE-D-17-22421 [pii]
PST - epublish
SO  - PLoS One. 2017 Dec 19;12(12):e0188427. doi: 10.1371/journal.pone.0188427.
      eCollection 2017.