IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques

Enrico Lugli, Yvonne M. Mueller, Mark G. Lewis, Francois Villinger, Peter D. Katsikis, Mario Roederer

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)2520-2529
Number of pages10
Issue number9
Publication statusPublished - Sep 1 2011


ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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