Cytotoxic T cells infiltrating a glioma express an aberrant phenotype that is associated with decreased function and apoptosis.
Cancer Immunol Immunother
; 50(6): 285-92, 2001 Aug.
Article
en En
| MEDLINE
| ID: mdl-11570581
In this study, we report on novel alterations found in rat intracranial (i.c.) tumor-infiltrating T lymphocytes (TIL) that are indicative of T cell defects and death. FACS analysis showed that the cytotoxic T cells (CTL) infiltrating rat T9.F gliomas were CD3epsilon+, alphabetaTCR+, CD8alpha+, but CD8beta-. These lymphocytes also stained positive for the B cell-specific marker, CD45RA, as well as Annexin-V, signifying apoptotic changes. Functional and biochemical analyses were performed to assess whether the aberrant phenotype was linked to other defects. When CD8alpha+ TIL were purified and stimulated in vitro, their proliferative capacity was markedly diminished in comparison with CD3+CD8alpha+CD8beta+ T cells isolated from the spleens of naive, non tumor-bearing rats. Furthermore, the mean fluorescence intensity of surface CD3epsilon was dramatically reduced in the CD3+CD8alpha+CD8beta- TIL population as compared with CD3-CD8alpha+CD8beta+ TIL from the same tumor-bearing animal. Biochemical studies revealed that the expression of TCRzeta and LAT were reduced in lysates generated from CD8alpha-purified TIL with respect to CD8alpha-purified T cells from naive spleen. We believe that these degenerative changes are reflective of chronic T cell receptor ligation, because in vitro culture of rat splenocytes or purified T cells with ConA or anti-CD3 mAb induced the same alterations. In vitro, the downregulation of CD8beta could be inhibited by the caspase inhibitor, z-VAD. These results suggest that the aberrant CTL phenotype found in the TIL of glioma-bearing rats may be novel signals for their impending death and degenerating anti-tumor immune function.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Linfocitos T Citotóxicos
/
Linfocitos Infiltrantes de Tumor
/
Apoptosis
/
Glioma
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Cancer Immunol Immunother
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Alemania