Treatment with granulocyte colony-stimulating factor decreases the capacity of hematopoietic progenitor cells for generation of lymphocytes in human immunodeficiency virus-infected persons

J Infect Dis. 1999 Dec;180(6):1819-26. doi: 10.1086/315136.

Abstract

An obstacle to stem cell gene therapy for AIDS is the limited numbers of hematopoietic progenitors available. Granulocyte colony-stimulating factor (G-CSF) is used for mobilization of progenitors, but little is known about the functional characteristics of mobilized progenitors, and immature and T cell progenitors may not be mobilized. This study examined the effect of G-CSF on the function of progenitors. Ten human immunodeficiency virus-infected patients received G-CSF (filgrastim, 300 microgram/day) for 5 days. Absolute numbers of immature and T cell progenitors did not increase. The ability of CD34+ progenitor cells to generate lymphocytes was examined by use of thymic organ cultures. The mean number of lymphocytes generated per CD34+ cell on day 0 was 0.72 and on day 4 was 0.09 (P<.003). The number of CD4+ cells generated per CD34+ cell was significantly reduced after G-CSF treatment. Thus, G-CSF increased the number of mature progenitor cells but did not increase T cell progenitors.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / analysis
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Filgrastim
  • Flow Cytometry
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1*
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Recombinant Proteins
  • T-Lymphocytes / physiology*
  • Thymus Gland / immunology

Substances

  • Antigens, CD34
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Filgrastim