A selective impairment of the IL-2 system in lymphocytes of patients with glioblastomas: increased level of soluble IL-2R and reduced protein tyrosine phosphorylation.
The occurrence of brain tumors is associated with broad suppression of the immune system function; however, the mechanisms involved in this impairment are not fully characterized. In this study, we have examined mechanisms involved in diminished T lymphocyte reactivity in patients with glioblastomas as compared to patients with other types of brain tumors. We found that the proliferative response of T lymphocytes stimulated with phytohemagglutinin or anti-CD3 was significantly reduced in these patients as compared to patients with meningiomas, oligodendrogliomas and healthy individuals. Stimulated T cells appear to express lower levels of the alpha-subunit (p55) of the IL-2 receptor (IL-2R), and increased levels of soluble IL-2R in cell supernatants, whereas no significant differences were observed in the level of the beta (p75)- or gamma-subunits. In addition, we found that competent T cells of glioblastoma patients exhibit lower levels of tyrosine phosphorylation in response to IL-2 as compared with cells of healthy donors. The decrease in the levels of IL-2 and its receptor was selective since no significant changes were observed in the secretion of other Th1- and Th2-derived cytokines (IFN-gamma and IL-4) and the expression of their respective receptors. These results indicate that the diminished response of T cells obtained from patients with glioblastomas may be due to a selective defect in the production of IL-2 and in the expression of functional IL-2R due to a decreased expression of the membranal IL-2R alpha and to lower levels of tyrosine phosphorylation in response to IL-2.
Ashkenazi
E
E
Department of Neurosurgery, Hadassaa Hospital, Jerusalem, Israel.
Deutsch
M
M
Tirosh
R
R
Weinreb
A
A
Tsukerman
A
A
Brodie
C
C
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005909:Glioblastoma / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D011506:Proteins; D015375:Receptors, Interleukin-2; D014443:Tyrosine