Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques.
The loss of CD4(+) T cells and the impairment of CD8(+) T cell function in HIV infection suggest that pharmacological treatment with IL-7 and IL-15, cytokines that increase the homeostatic proliferation of T cells and improve effector function, may be beneficial. However, these cytokines could also have a detrimental effect in HIV-1-infected individuals, because both cytokines increase HIV replication in vitro. We assessed the impact of IL-7 and IL-15 treatment on viral replication and the immunogenicity of live poxvirus vaccines in SIV(mac251)-infected macaques (Macaca mulatta). Neither cytokine augmented the frequency of vaccine-expanded CD4(+) or CD8(+) memory T cells, clonal recruitment to the SIV-specific CD8(+) T cell pool, or CD8(+) T cell function. Vaccination alone transiently decreased the viral set point following antiretroviral therapy suspension. IL-15 induced massive proliferation of CD4(+) effector T cells and abrogated the ability of vaccination to decrease set point viremia. In contrast, IL-7 neither augmented nor decreased the vaccine effect and was associated with a decrease in TGF-beta expression. These results underscore the importance of testing immunomodulatory approaches in vivo to assess potential risks and benefits for HIV-1-infected individuals.
Hryniewicz
Anna
A
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Building 41, Bethesda, MD 20892, USA.
Price
David A
DA
Moniuszko
Marcin
M
Boasso
Adriano
A
Edghill-Spano
Yvette
Y
West
Sadie M
SM
Venzon
David
D
Vaccari
Monica
M
Tsai
Wen-Po
WP
Tryniszewska
Elzbieta
E
Nacsa
Janos
J
Villinger
Francois
F
Ansari
Aftab A
AA
Trindade
Christopher J
CJ
Morre
Michel
M
Brooks
David
D
Arlen
Philip
P
Brown
Helen J
HJ
Kitchen
Christina M R
CM
Zack
Jerome A
JA
Douek
Daniel C
DC
Shearer
Gene M
GM
Lewis
Mark G
MG
Koup
Richard A
RA
Franchini
Genoveffa
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014766:Viremia / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D019409:Interleukin-15; D015851:Interleukin-7; D018449:SAIDS Vaccines; D016212:Transforming Growth Factor beta