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

• Published in: Clinical and experimental immunology Vol. 108; no. 2; pp. 243 - 250
• Main Authors: KIM, J. H., LOVELAND, J. E., SITZ, K. V., RATTO KIM, S., MCLINDEN, R. J., TENCER, K., DAVIS, K., BURKE, D. S., BOSWELL, R. N., REDFIELD, R. R., BIRX, D. L.
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.05.1997; Blackwell; Blackwell Science Inc
• Subjects: Adjuvants, Immunologic - pharmacology; AIDS Vaccines - immunology; AIDS/HIV; Biological and medical sciences; Cohort Studies; Female; HIV Core Protein p24 - biosynthesis; HIV Core Protein p24 - immunology; HIV Envelope Protein gp160 - immunology; HIV Infections - immunology; HIV-1 - immunology; HIV‐1; human immunodeficiency virus 1; Humans; IL‐12; IL‐7; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Interleukin-12 - pharmacology; Interleukin-7 - pharmacology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation - drug effects; Male; Medical sciences; Original; T cell; Tetanus Toxoid - immunology; Vaccines, Synthetic - immunology; Human; Immunopathology; Immune response; HIV-1 virus; Retroviridae; Interleukin 12; AIDS; Cellular immunity; Vaccine; Immune deficiency; Active immunization; Infection; Virus; Interleukin 7; Treatment; Viral disease; Immunotherapy; T-Lymphocyte; Lentivirinae; Human immunodeficiency virus; Virus envelope
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1997.d01-1006.x

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.