title: Elevated interleukin-7 levels not sufficient to maintain T-cell homeostasis during simian immunodeficiency virus-induced disease progression.
abstract: Elevated levels of interleukin 7 (IL-7) have been correlated with various T-cell depletion conditions, including HIV infection, and suggested as an indicator of HIV disease progression (AIDS and death). Here, the assessment of pathogenic simian immunodeficiency virus (SIVmac239) infection in rhesus macaques demonstrated a clear association between a significant elevation in IL-7 levels and disease progression. In 5 macaques that progressed to simian AIDS and death, elevated IL-7 levels were unable to restore T-cell homeostasis. In contrast, increased IL-7 levels were followed by relatively high and stable T-cell numbers in the SIV-infected macaques with a slow-progressing phenotype. Further, studies in sooty mangabeys that do not progress to simian AIDS and that maintain stable T-cell numbers despite high levels of viral replication support the importance of IL-7 and T-cell homeostasis in disease progression. These data suggest that during pathogenic SIV infection with high viral replication, elevated IL-7 levels are unable to recover T-cell homeostasis, thereby leading to disease progression. The utility of IL-7 as a potential immunotherapeutic agent to improve HIV/SIV-related T-cell depletion may therefore depend on controlling the pathogenic effects of viral replication prior to the administration of IL-7.
authors.affiliation: University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
authors.forename: Alagarraju
authors.initials: A
authors.lastname: Muthukumar
authors.forename: Aneta
authors.initials: A
authors.lastname: Wozniakowski
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gauduin
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Harold M
authors.initials: HM
authors.lastname: McClure
authors.forename: R Paul
authors.initials: RP
authors.lastname: Johnson
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
mesh_terms: D000818:Animals; D002455:Cell Division; D016665:Cercocebus atys; D006706:Homeostasis; D006801:Humans; D015851:Interleukin-7 / Q000097:blood*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014779:Virus Replication
chemical_list: D015851:Interleukin-7