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Role of IL-15 Signaling in the Pathogenesis of Simian Immunodeficiency Virus Infection in Rhesus Macaques
- Source :
- J Immunol
- Publication Year :
- 2019
- Publisher :
- The American Association of Immunologists, 2019.
-
Abstract
- Although IL-15 has been implicated in the pathogenic hyperimmune activation that drives progressive HIV and SIV infection, as well as in the generation of HIV/SIV target cells, it also supports NK and T cell homeostasis and effector activity, potentially benefiting the host. To understand the role of IL-15 in SIV infection and pathogenesis, we treated two cohorts of SIVmac239-infected rhesus macaques (RM; Macaca mulatta), one with chronic infection, the other with primary infection, with a rhesusized, IL-15–neutralizing mAb (versus an IgG isotype control) for up to 10 wk (n = 7–9 RM per group). In both cohorts, anti–IL-15 was highly efficient at blocking IL-15 signaling in vivo, causing 1) profound depletion of NK cells in blood and tissues throughout the treatment period; 2) substantial, albeit transient, depletion of CD8+ effector memory T cells (TEM) (but not the naive and central memory subsets); and 3) CD4+ and CD8+ TEM hyperproliferation. In primary infection, reduced frequencies of SIV-specific effector T cells in an extralymphoid tissue site were also observed. Despite these effects, the kinetics and extent of SIV replication, CD4+ T cell depletion, and the onset of AIDS were comparable between anti–IL-15– and control-treated groups in both cohorts. However, RM treated with anti–IL-15 during primary infection manifested accelerated reactivation of RM rhadinovirus. Thus, IL-15 support of NK cell and TEM homeostasis does not play a demonstrable, nonredundant role in SIV replication or CD4+ T cell deletion dynamics but may contribute to immune control of oncogenic γ-herpesviruses.
- Subjects :
- Male
T cell
Immunology
Cell
Simian Acquired Immunodeficiency Syndrome
Biology
Article
Pathogenesis
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Immunology and Allergy
Rhadinovirus
Interleukin-15
Effector
virus diseases
biology.organism_classification
Macaca mulatta
Chronic infection
medicine.anatomical_structure
Interleukin 15
Female
Simian Immunodeficiency Virus
CD8
Signal Transduction
030215 immunology
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 203
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....d8261ffa4e55bdea0264c899e1f0609d
- Full Text :
- https://doi.org/10.4049/jimmunol.1900792