Abstract
IL-15, a proinflammatory cytokine critical for the generation, maintenance, and homeostasis of T cell responses, is produced naturally in response to HIV/SIV infection, but has also demonstrated therapeutic potential. IL-15 can boost CD4+ and CD8+ T cell and NK cell proliferation, activation, and function. However, IL-15 treatment may cause aberrant immune activation and accelerated disease progression in certain circumstances. Moreover, the relationship between the timing of IL-15 administration and disease progression remains unclear. The IL-15 superagonist N-803 was developed to expand the therapeutic potential of IL-15 by maximizing its tissue distribution and half-life. N-803 has garnered enthusiasm recently as a way to enhance the innate and cellular immune responses to HIV/SIV by improving CD8+ T cell recognition and killing of virus-infected cells and directing immune cells to mucosal sites and lymph nodes, the primary sites of virus replication. N-803 has also been evaluated in “shock and kill” strategies due to its potential to reverse latency (shock) and enhance antiviral immunity (kill). This review examines the current literature about the effects of IL-15 and N-803 on innate and cellular immunity, viral burden, and latency reversal in the context of HIV/SIV, and their therapeutic potential both alone and combined with additional interventions such as antiretroviral therapy (ART) and vaccination.
Highlights
IL-15, a proinflammatory cytokine critical for the generation, maintenance, and homeostasis of T cell responses, is produced naturally in response to human immunodeficiency virus (HIV)/SIV infection, but has demonstrated therapeutic potential
This review examines the current literature about the effects of IL-15 and N-803 on innate and cellular immunity, viral burden, and latency reversal in the context of HIV/SIV, and their therapeutic potential both alone and combined with additional interventions such as antiretroviral therapy (ART) and vaccination
HIV-infected individuals progress to acquired immunodeficiency syndrome (AIDS), which is characterized by increasing plasma viremia and corresponding depletion of CD4+ T cells through complex immune dysfunction including CD4+ T cell death and CD8+ T cell activation and expansion [5,6,7,8]
Summary
Cytotoxic CD8+ T cells play a crucial role in responding to viral infections such as human immunodeficiency virus (HIV). I IFN signaling has been shown abundantly in a wide variety of tissues, such as skeletal muscle types, including epithelial cells, monocytes, macrophages, and protein expression is heavily regulated by multiple negative fe aberrant immune activation and auto in response to expression infections such asIL-15Rα. T ce fector cells capable of expansion and pathogen reco been shown to increase both the expression the IL-15Rα subunit, as well as the excessi cytotox signaling promotes beneficial innate and adaptive immune responses, includi naling. IL-15 production, expression, signaling, must be ca uated forability the ability toworsening promote both and Idetrimental immunomodulatory uated efforthey the ability to pr to tion, promote both beneficial and detrimental immunomodulatory effects throughout in response to infections such as HIV/SIV, and they can induc are typically thought of asthroughout innate immune cyt facets ofType adaptive immunity, including been shown to increase both the expre ing chronic. Both free IL-15 and IL-15 agonist complexes are being studied preclinically and clinically for their immunotherapeutic potential
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
