title: IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques.
abstract: Human immunodeficiency virus (HIV) infection is characterized by a progressive loss of memory CD4(+) T cells in multiple tissues, especially at mucosal surfaces where most of these cells reside. Although antiretroviral therapy (ART) suppresses viral replication and promotes the recovery of peripheral CD4(+) T cells, HIV-infected patients fail to fully reconstitute the CD4(+) T-cell pool at mucosal sites. IL-15 has been shown to preferentially expand memory-phenotype T cells and promote their migration to nonlymphoid tissues. Here we examined IL-15 treatment in combination with highly active ART in chronically SIV-infected rhesus macaques and found that IL-15 delayed viral suppression and failed to enhance ART-induced total and antigen-specific CD4(+) T-cell reconstitution at mucosal and lymphoid sites. IL-15 was able to induce the transient proliferation of SIV-specific, CMV-specific, and total memory CD8(+) T cells, but not of SIV-specific or total CD4(+) T cells. Moreover, upon treatment interruption, macaques receiving combined IL-15+ART lost CD4(+) T cells faster than those receiving ART alone. These results suggest that the combination of IL-15 with highly active ART is not more efficient than ART alone in promoting CD4(+) T-cell recovery in HIV-infected individuals and may accelerate CD4+ T-cell loss after treatment interruption.
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Enrico
authors.initials: E
authors.lastname: Lugli
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Mueller
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Peter D
authors.initials: PD
authors.lastname: Katsikis
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D018928:Immunity, Mucosal / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007167:Immunotherapy; D019409:Interleukin-15 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D011897:Random Allocation; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D007155:Immunologic Factors; D019409:Interleukin-15; D063065:Organophosphonates; D011760:Pyrrolidinones; D003841:Deoxycytidine; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine