Apoptotic elimination of peripheral T lymphocytes in patients with primary intracranial tumors.
OBJECTIVE
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 that 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 alpha, or tumor necrosis factor-beta (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.
Morford
L A
LA
Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Dix
A R
AR
Brooks
W H
WH
Roszman
T L
TL
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001932:Brain Neoplasms / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005909:Glioblastoma / Q000276:immunology; D005910:Glioma / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D020298:U937 Cells / Q000276:immunology
D016207:Cytokines