V(delta)1 T Lymphocytes May Play Role in Curbing CLL

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Cancer Res. 2004 Dec 15;64(24):9172-9179.

V{delta}1 T Lymphocytes from B-CLL Patients Recognize ULBP3 Expressed

on Leukemic B Cells and Up-Regulated by Trans-Retinoic Acid.

Poggi A, Venturino C, Catellani S, Clavio M, Miglino M, Gobbi M,

Steinle A, Ghia P, Stella S, Caligaris-Cappio F, Zocchi MR.

Laboratory of Immunology, National Cancer Research Institute, Genoa,

Italy.

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.

PMID: 15604289 [PubMed - as supplied by publisher]