Polyclonal T Lymphocytes Transform into Malignant Cells by Retroviral Mediated Transfer of p21SNFT Gene

Abstract

Background: p21SNFT (21 kDa small nuclear factor isolated from T cells) gene is known to be increasingly expressed in the cells of Hodgkin disease and Hodgkin cell lines. It was not investigated before if this gene had any effect on polyclonal T lymphocytes. For this purpose, we transduced this gene into polyclonal T lymphocytes and transplanted into mice.Materials and Methods: We used γ-retroviral vector to transduce this gene into polyclonal T lymphocytes, isolated from wild type black-6 mice. After confirmation of p21SNFT expression via marker gene eGFP (enhanced green fluorescent protein) and Western blot analysis, these cells were transplaned into immunocompromised Rag 1 deficient mice. The control group of mice was transplanted with γ-retroviral vector, carrying only marker gene (eGFP). The mice were followed up. The results showed that all 7 mice transplanted with p21SNFT-carrying polyclonal T lymphocytes developed massively enlarged mesenteric lymph nodes after 435 to 550 days of transplantation.Results: Histopathological analyses of these lymph nodes revealed the lymphoma, which resembled human peripheral T cell lymphoma type. Furthermore, immunophenotyping of tumor cells by FACS analysis revealed loss of T cell markers and expression of CD19 marker. From the control group, all five mice remained healthy and did not develop any tumor.Conclusion: The study concludes that γ-retroviral mediated transfer of p21SNFT transforms polyclonal T lymphocytes into malignant cells.

Keywords: γ-retroviral vector; Lymphoma; Malignant transformation; p21SNFT; T lymphocytes