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 Blood, 1 March 2007, Vol. 109, No. 5, pp. 2078-2085.
Prepublished online as a Blood First Edition Paper on September 14, 2006; DOI 10.1182/blood-2006-06-028985.

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IMMUNOBIOLOGY

Expansion of V{delta}1 T lymphocytes producing IL-4 in low-grade non-Hodgkin lymphomas expressing UL-16–binding proteins

Silvia Catellani1, Alessandro Poggi2, Andrea Bruzzone3, Patrizia Dadati4, Jean Louis Ravetti4, Marco Gobbi5, and Maria Raffaella Zocchi6

1 Laboratory of Hematology, University of Genoa, Genoa, Italy; 2 Experimental Oncology D, National Institute for Cancer Research, Genoa, Italy; 3 Department of Internal Medicine, University of Genoa, Genoa, Italy; 4 Department of Pathology, San Martino Hospital, University of Genoa, Genoa, Italy; 5 Laboratory of Clinical Hematology, University of Genoa, Genoa, Italy; and 6 Laboratory of Tumor Immunology, San Raffaele Scientific Institute, Milan, Italy.

Data on 23 patients with low-grade non-Hodgkin lymphomas (NHLs), 4 mantle (MT), 4 marginal zone (MZ), and 15 follicular (FL), were analyzed and compared with 10 high-risk (HR) B-cell chronic lymphocytic leukemias (B-CLLs) with lymph node involvement and 4 diffuse large-cell lymphomas (DLCLs). A significant increase in circulating V{delta}1 T lymphocytes producing interleukin-4 (IL-4) was found in patients with FL, MT, and MZ NHL, at variance with DLCL and HR B-CLL. IL-4 was also detectable in the sera and lymph nodes of the same patients. In 19 of the 23 patients with NHL with increased circulating V{delta}1 T lymphocytes, B cells expressing the UL-16–binding proteins (ULBPs) ULBP2 or ULBP3 or both were found in peripheral blood, bone marrow, or lymph nodes. Of note, in HR B-CLL or in DLCL, where leukemic cells were negative for ULBPs, no V{delta}1 T-cell increase was found. Moreover, V{delta}1 T lymphocytes from patients with FL NHL proliferate in response to ULBP2+ and ULBP3+ lymphoma cells. Finally, patients with high expression of ULBPs, increased circulating V{delta}1 T lymphocytes, and high levels of serum IL-4 showed stable disease in a 1-year follow-up in contrast to patients with low circulating V{delta}1 T cells and undetectable IL-4 or ULBPs.


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