PMID- 9379040
OWN - NLM
STAT- MEDLINE
DCOM- 19971112
LR  - 20071115
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 159
IP  - 9
DP  - 1997 Nov 1
TI  - T cell receptor-mediated signaling is defective in T cells obtained from patients 
      with primary intracranial tumors.
PG  - 4415-25
AB  - It has been well established that patients with malignant glioblastomas exhibit T 
      cell anergy. In this report, we further investigate the nature of this T cell 
      anergy. The results demonstrate that tumor size but not location correlates with 
      decreased mitogen or anti-CD3 mAb responsiveness of T cells obtained from 
      patients. Stimulation of the TCR/CD3 complex on these patients' T cells revealed 
      defects in early transmembrane signaling. Both PHA and anti-CD3 mAb activated PBL 
      and T cells obtained from patients exhibited a marked decrease in the tyrosine 
      phosphorylation of a number of proteins. In particular, decreased phosphorylation 
      of pp100 and phospholipase Cgamma1 (PLCgamma1) was observed. In addition, 
      PLCgamma1 and p56(lck) protein levels were dramatically reduced in T cells 
      obtained from patients harboring a glioma. In contrast, the protein levels of 
      p59(fyn) were normal or only slightly reduced in T cells obtained from patients 
      with gliomas. Quantitation of free intracellular calcium concentrations ([Ca2+]i) 
      after mitogen (PHA) stimulation or ionomycin treatment of T cells obtained from 
      patients revealed that they mobilize less calcium than do T cells obtained from 
      normal subjects. Stimulation of T cells obtained from patients with PMA and 
      ionomycin, which should bypass the requirement for PLCgamma1 activation as well 
      as directly activate the p21(ras) signaling pathway, did not restore the 
      proliferative capacity of these T cells to normal levels. These results indicate 
      that the anergy observed in T cells obtained from these patients is a consequence 
      of one or more defects in the early transmembrane signaling events associated 
      with TCR/CD3 stimulation.
FAU - Morford, L A
AU  - Morford LA
AD  - Department of Microbiology and Immunology, The University of Kentucky Medical 
      Center, Lexington 40536-0084, USA.
FAU - Elliott, L H
AU  - Elliott LH
FAU - Carlson, S L
AU  - Carlson SL
FAU - Brooks, W H
AU  - Brooks WH
FAU - Roszman, T L
AU  - Roszman TL
LA  - eng
GR  - CA18234/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - EC 3.1.4.- (Type C Phospholipases)
SB  - IM
MH  - Brain Neoplasms/*immunology/pathology
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/immunology
MH  - Glioma/*immunology/pathology
MH  - Humans
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - Signal Transduction/*immunology
MH  - T-Lymphocytes/*immunology
MH  - Type C Phospholipases/immunology
EDAT- 1997/10/31 00:00
MHDA- 1997/10/31 00:01
CRDT- 1997/10/31 00:00
PHST- 1997/10/31 00:00 [pubmed]
PHST- 1997/10/31 00:01 [medline]
PHST- 1997/10/31 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1997 Nov 1;159(9):4415-25.