IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection

Blood. 2009 Jun 18;113(25):6304-14. doi: 10.1182/blood-2008-10-186601. Epub 2009 Apr 20.

Abstract

Interleukin 7 (IL-7) is a common gamma chain receptor cytokine implicated in thymopoiesis and in peripheral expansion and survival of T lymphocytes. The safety and activity of recombinant human IL-7 (rhIL-7) administration were therefore examined in HIV-infected persons. In this prospective randomized placebo-controlled study, a single subcutaneous dose of rhIL-7 was well tolerated with biologic activity demonstrable at 3 microg/kg and a maximum tolerated dose of 30 microg/kg. Injection site reactions and transient elevations of liver function tests were the most notable side effects. Transient increases in plasma HIV-RNA levels were observed in 6 of 11 IL-7-treated patients. Recombinant hIL-7 induced CD4 and CD8 T cells to enter cell cycle; cell-cycle entry was also confirmed in antigen-specific CD8 T cells. Administration of rhIL-7 led to transient down-regulation of the IL-7 receptor alpha chain (CD127) in both CD4(+) and CD8(+) T cells. Single-dose rhIL-7 increased the numbers of circulating CD4(+) and CD8(+) T cells, predominantly of central memory phenotype. The frequency of CD4(+) T cells with a regulatory T-cell phenotype (CD25(high) CD127(low)) did not change after rhIL-7 administration. Thus, rhIL-7 has a biologic and toxicity profile suggesting a potential for therapeutic trials in HIV infection and other settings of lymphopenia. This clinical trial has been registered at http://www.clinicaltrials.gov under NCT0099671.

Trial registration: ClinicalTrials.gov NCT00099671 NCT00099671.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Cycle / drug effects
  • Chemical and Drug Induced Liver Injury / etiology
  • Down-Regulation / drug effects
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1*
  • Humans
  • Immunologic Memory / drug effects
  • Interleukin-7 / administration & dosage
  • Interleukin-7 / adverse effects
  • Interleukin-7 / blood
  • Interleukin-7 / pharmacology
  • Interleukin-7 / therapeutic use*
  • Interleukin-7 Receptor alpha Subunit / biosynthesis
  • Interleukin-7 Receptor alpha Subunit / genetics
  • Lymphocyte Count
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / blood
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Viral Load

Substances

  • IL7 protein, human
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit
  • Recombinant Proteins

Associated data

  • ClinicalTrials.gov/NCT00099671
  • ClinicalTrials.gov/NCT00099671