ABSTRACT
The ability to genetically modify T cells is a critical component to many immunotherapeutic strategies and research studies. However, the success of these approaches is often limited by transduction efficiency. As retroviral vectors require cell division for integration, transduction efficiency is dependent on the appropriate activation and culture conditions for T cells. Naive CD8(+) T cells, which are quiescent, must be first activated to induce cell division to allow genetic modification. To optimize this process, we activated mouse T cells with a panel of different cytokines, including interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL-12, IL-15 and IL-23, known to act on T cells. After activation, cytokines were removed, and activated T cells were retrovirally transduced. We found that IL-12 preconditioning of mouse T cells greatly enhanced transduction efficiency, while preserving function and expansion potential. We also observed a similar transduction-enhancing effect of IL-12 preconditioning on human T cells. These findings provide a simple method to improve the transduction efficiencies of CD8(+) T cells.
Subject(s)
CD8-Positive T-Lymphocytes/physiology , Interleukin-12/pharmacology , Moloney murine leukemia virus/genetics , Transduction, Genetic , Animals , B-Cell Lymphoma 3 Protein , CD8-Positive T-Lymphocytes/drug effects , Cells, Cultured , Gene Expression , Humans , Mice, Inbred C57BL , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
A 36-year-old male presented with symptomatic left renal mass simulating renal cell carcinoma. He underwent left radical nephrectomy and histopathology revealed chronic renal infarct with calcifications. The case description warrants the inclusion of focal chronic renal infarcts in the differential diagnosis of renal masses, especially following history of previous trauma.