Apoptotic elimination of peripheral T lymphocytes in patients with primary intracranial tumors

Lorri A. Morford, Amy R. Dix, William H. Brooks, Thomas L. Roszman

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Object. Patients with gliomas exhibit severe T lymphopenia during the course of the disease. This study was conducted to determine the mechanism(s) responsible for the lymphopenia. Methods. Using two-color fluorescent staining techniques, the authors show thai significant numbers of T cells undergo apoptosis in the peripheral blood of patients with gliomas. To determine whether a glioma-derived factor(s) induces this apoptosis, rosette- purified T cells obtained from healthy donors were treated with glioma cell culture supernatant (GCCS) and examined for apoptosis. It is demonstrated that treatment of normal T cells with GCCS induced apoptosis only with concurrent stimulation of the T-cell receptor/CD3 complex. The addition of neutralizing antibodies to interleukin (IL)-10, IL-4, transforming growth factor-α, or tumor necrosis factor-β (lymphotoxin) did not rescue these T cells from apoptosis. Experiments were also conducted in which the degree of monocyte involvement in the induction of T-cell apoptosis was explored. The U937 cells were pretreated for 20 hours with a 1:20 dilution of GCCS. After the removal of GCCS, the U937 cells were cultured in transwell assays with stimulated T cells. Although control U937 cells did not induce apoptosis of the activated T cells, GCCS-pretreated U937 cells induced appreciable apoptosis in normal, stimulated T-cell cultures. Conclusions. These data indicate that one mechanism by which gliomas cause immunosuppressive effects is the induction of monocytes to release soluble factors that promote activated T-cell apoptosis. The loss of activated T cells leads to T lymphopenia and contributes to the deficiencies in cell-mediated immunity that have been observed during testing of glioma patients' immune function.

Original languageEnglish
Pages (from-to)935-946
Number of pages12
JournalJournal of Neurosurgery
Volume91
Issue number6
DOIs
StatePublished - Dec 1999

Keywords

  • Apoptosis
  • Cytokine
  • Glioma
  • Monocyte
  • T lymphocyte

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Fingerprint

Dive into the research topics of 'Apoptotic elimination of peripheral T lymphocytes in patients with primary intracranial tumors'. Together they form a unique fingerprint.

Cite this