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IBL4, A B cell line derived from an AIDS-related lymphoma, is a novel tumor stimulator and target for Vy2Vd2 T cell

Vg2Vd2 T cells are the predominant peripheral blood subset of – T cells and recognize tumor cells in a TCR-dependent, MHC-unrestricted manner. Following HIV infection there is a rapid and targeted depletion of circulating, anti-tumor Vy2Vd2 T cells with concomitant increases in B cell lymphoma incidence. We hypothesized that the specific depletion of Vy2Vd2 T cells after HIV compromises an important tumor surveillance system and directly contributes to the increased incidence of B cell lymphoma observed in HIV-positive cohorts. To test this hypothesis we collected tumor cell lines derived from clinical cases of AIDS-related lymphoma and tested them for susceptibility to Vy2Vd2 cytotoxicity and ability to stimulate Vy2Vd2 T cell proliferation from PBMC in vitro. Several tumor cell lines including Daudi, KSY1 and IBL4 were recognized and lysed by polyclonal Vy2Vd2 T cell effectors in a dose-dependent manner. We screened several irradiated AIDS-derived tumor lines in vitro for the capacity to stimulate Vy2Vd2 T cells and identified IBL4 as a novel tumor stimulator for the Vy2Vd2 subset that skewed the Vy2 repertoire toward longer chain lengths without affecting the overall distribution of Vy2 chain lengths and without obvious tumor-specific CDR3 sequences commonality among responding blood donors. These data provide important insight into tumor recognition by Vy2Vd2 T cells and justify chemotherapeutic approaches using alkylphosphate stimulation to boost the frequency and tumor effector function of circulating Vy2Vd2 lymphocytes.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Hebbeler, A., Cummings, JS., Cairo, C. et al. IBL4, A B cell line derived from an AIDS-related lymphoma, is a novel tumor stimulator and target for Vy2Vd2 T cell. Retrovirology 3 (Suppl 1), P24 (2006).

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