Molecular and functional analysis of γδ T cell expansions in immunodeficient patients

Abstract

Methods and results Two adult patients with thymoma and γδ T cell expansions were studied by flow cytometry and T cell receptor γand δ-chain spectratyping. One patient suffering from leishmaniasis and thymic carcinoma showed a peculiar polyclonal γδ T cell proliferation while another patient with a benign thymoma and CMV reactivation had a persistent oligoclonal amplification of γδ T cells. In one pediatric patient with incomplete RAG-1 deficiency, we found a restricted variability of the expressed Vδ3, versus Vδ1 and Vδ2 chains and a seemingly monoclonal usage of the Vγ4 element. Sequencing revealed that these γδ T cells showed significant junctional diversity. These data suggested selection of the γδ T cells by antigens such as CMV infection. Indeed, 4 out of 5 δ T cell clones that could be derived from this patient secreted TNFα in response to CMV infected allogeneic fibroblasts.