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


Patients with various forms of immunodeficiencies frequently show expansions of γδ T cells in their peripheral blood. We attempted to characterize the γδ T cell subpopulations in these patients and possibly elucidate the cellular mechanisms involved in the γδ T cell expansions in some of these patients.

Methods and results

Two adult patients with thymoma and γδ T cell expansions were studied by flow cytometry and T cell receptor γ- and 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.


Overall, studies of human γδ T cells under the conditions of a limited immune system imply two non-exclusive explanations for the γδ T cell predominance in immunodeficiencies: a) a developmental advantage of γδ T cells, possibly by a less stringent T cell development than for αβ T cells and b) a proliferative response caused by infectious or autoantigen-driven peripheral stimulations, such as CMV infections.

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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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Fisch, P., Christopoulos, P., Nikolopoulos, E. et al. Molecular and functional analysis of γδ T cell expansions in immunodeficient patients. Diagn Pathol 2 (Suppl 1), S8 (2007).

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