Vdelta1 T lymphocytes from B-CLL patients recognize ULBP3 expressed on leukemic B cells and up-regulated by trans-retinoic acid.
Cancer Res
; 64(24): 9172-9, 2004 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-15604289
We analyzed 38 untreated patients with chronic lymphocytic leukemia of B-cell type (B-CLL): 24 low-, 8 intermediate-, and 6 high-risk stage. In 15 patients (13 low risk and 2 intermediate risk), circulating Vdelta1 T lymphocytes were significantly increased (100 to 300 cells/muL) compared with most intermediate, all high-risk stage, and 15 healthy donors (50 to 100 cells/muL). We studied these Vdelta1 T lymphocytes and observed that they proliferated in vitro and produced tumor necrosis factor alpha or IFN-gamma in response to autologous leukemic B cells but not to normal lymphocytes. However, they were unable to kill resting autologous B cells, which lack the MHC-related MIC-A antigen and express low levels of the UL16-binding protein (ULBP) 3 and undetectable levels of ULBP1, ULBP2, and ULBP4. All these molecules are reported ligands for the NKG2D receptor, which is expressed by gammadelta T cells and activates their cytolytic function. The Vdelta1 T lymphocytes studied were able to lyse the ULBP3(+) C1R B-cell line upon transfection with MIC-A. More importantly, they also lysed autologous B-CLL cells when transcription and expression of MIC-A or up-regulation of ULBP3 were achieved either by activation or by exposure to trans-retinoic acid. The NKG2D receptor expressed on Vdelta1 T cells was involved in the recognition of B-CLL. Finally, in six patients with low numbers of circulating Vdelta1 T cells and undetectable ULBP3, the disease progressed over 1 year, whereas no progression occurred in patients with high Vdelta1 T lymphocytes and detectable/inducible ULBP3. These data suggest that Vdelta1 T lymphocytes may play a role in limiting the progression of B-CLL.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tretinoina
/
Linfocitos B
/
Linfocitos T
/
Antígenos de Histocompatibilidad Clase I
/
Leucemia Linfocítica Crónica de Células B
/
Proteínas Portadoras
/
Receptores de Antígenos de Linfocitos T gamma-delta
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cancer Res
Año:
2004
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos