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

J. H. Kim, J. E. Loveland, K. V. Sitz, S. Ratto Kim, R. J. Mclinden, K. Tencer, K. Davis, D. S. Burke, R. N. Boswell, R. R. Redfield, D. L. Birx

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)243-250
Number of pages8
JournalClinical and Experimental Immunology
Volume108
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • HIV-1
  • IL-12
  • IL-7
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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