Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1.
The failure of immune effector mechanisms to control HIV-1 infection has important consequences for the human host. In a randomized cohort of HIV-infected patients, there was striking in vitro restriction of the proliferative response to HIV-1 envelope protein (Env), gp160; only 34% of patients recognized Env. Therapeutic vaccination with recombinant gp160 or gp120 (rgp160, rgp120) reversed the restriction in vitro, with Env recognition rising to 81%. Peripheral blood mononuclear cells (PBMC) from HIV-infected vaccine recipients, placebo recipients, and seronegative volunteers were cultured with exogenous IL-7 or IL-12 and either tetanus toxoid (TT) or gp160. IL-7 significantly augmented proliferative responses to TT and gp160, whereas IL-12 only affected proliferation to gp160. IL-7, but not IL-12, increased the number of HIV-infected placebo recipients who recognized rgp160. IL-12 had its greatest effect in the induction of rgp160-specific responses from seronegative individuals. The data suggest that these two cytokines have differential activity in the relief of restricted cellular immunity to Env; the predominant effect of IL-7 is in individuals who have been primed by exposure to antigen, while the effect of IL-12 is most evident in seronegative, unprimed individuals. Modification of restricted proliferative responses to Env by vaccination or cytokines in vitro suggests that strategies incorporating IL-7 or IL-12 as adjuvants may selectively boost cellular reactivity to HIV-1.
Kim
J H
JH
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD, USA.
Loveland
J E
JE
Sitz
K V
KV
Ratto Kim
S
S
Mclinden
R J
RJ
Tencer
K
K
Davis
K
K
Burke
D S
DS
Boswell
R N
RN
Redfield
R R
RR
Birx
D L
DL
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D015331:Cohort Studies; D005260:Female; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D013745:Tetanus Toxoid / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016655:HIV Core Protein p24; D019302:HIV Envelope Protein gp160; D015851:Interleukin-7; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; D018664:Interleukin-12