FcRgamma chain does not replace CD3zeta chain in CD3zeta-deficient T lymphocytes of patients with gastric adenocarcinoma.
Defective CD3zeta chain expression has been reported in T lymphocytes of patients with inflammatory diseases, such as systemic lupus erythematosus or osteoarthritis, and with cancer. In lupus, the absent CD3zeta chain is replaced by the FcRgamma chain, rendering the T cells hyper responsive. However, there are no data on T lymphocytes from patients with cancer. In this study, the presence of the FcRgamma chain and its associated kinase, Syk, was analysed in patients with gastric adenocarcinoma and healthy subjects. Western blot and immunoprecipitation experiments were carried out with total cell or lipid raft extracts from fresh peripheral blood mononuclear cells or T lymphocytes, and Herpesvirus saimiri-derived T-cell lines (of blood or tissue origin). Our results revealed that the absent CD3zeta chain in cancer T lymphocytes was not replaced by FcRgamma either in fresh T cells or T-cell lines, in contrast to lupus T cells. This altered expression of signalling molecules in T lymphocytes of cancer patients, would explain their low proliferative capacity. Our T-cell lines represent tools to unveil the signalling abnormalities of cancer T lymphocytes.
Lopez-Santalla
Mercedes
M
Inmunologia, Facultad de Medicina, Universidad Complutense de Madrid, Pabellon 5, 4(a) planta, 28040 Madrid, Spain.
Krishnan
Sandeep
S
Valeri
Anna P
AP
Aguilera-Montilla
Noemi
N
Fisher
Carolyn U
CU
Perez-Blas
Mercedes
M
Gutierrez-Calvo
Alberto
A
Lasa
Inmaculada
I
Granell-Vicent
Javier
J
Tsokos
George C
GC
Martin-Villa
José M
JM
D000230:Adenocarcinoma / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002457:Cell Extracts; D002471:Cell Transformation, Neoplastic; D006567:Herpesvirus 2, Saimiriine; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology*; D013274:Stomach Neoplasms / Q000276:immunology*; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D002457:Cell Extracts; D047908:Intracellular Signaling Peptides and Proteins; D011961:Receptors, Fc; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase