Consequences of stable transduction and antigen-inducible expression of the human interleukin-7 gene on tetanus-toxoid-specific T cells

• Published in: Human gene therapy Vol. 5; no. 12; p. 1457
• Main Authors: Kim, J H, Ratto, S, Sitz, K V, Mosca, J D, McLinden, R J, Tencer, K L, Vahey, M T, St Louis, D, Birx, D L, Redfield, R R
• Format: Journal Article
• Language: English
• Published: United States 01.12.1994
• Subjects: Animals; Base Sequence; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cell Line; Cytokines - biosynthesis; Gene Expression Regulation; Genetic Vectors; Humans; Interleukin-7 - biosynthesis; Interleukin-7 - genetics; Mice; Molecular Sequence Data; Retroviridae - genetics; Tetanus Toxoid - immunology; Transduction, Genetic
• ISSN: 1043-0342
• DOI: 10.1089/hum.1994.5.12-1457

Interleukin-7 (IL-7) has previously been shown to increase antigen-specific immune responses; the effect of IL-7 on human antigen-specific T cell lines has not directly been addressed. A tetanus-toxoid (TT)-specific T cell line exhibited increased proliferation in the presence of exogenous IL-7, suggesting that IL-7 may be useful in the potentiation of immune responses to defined microbial antigens. Murine retroviral vectors encoding the human IL-7 gene and the neomycin phosphotransferase gene (neoR) were packaged into murine retroviral particles, and supernatants containing these retroviral vectors were used to infect a CD4+ lymphoblastoid cell line. Stable integration of the retroviral vector and constitutive expression of the IL-7 gene were observed. Successful IL-7 gene transduction into TT-specific T cells was also accomplished. Detection of neoR DNA sequences and expression of IL-7-specific mRNA increased with selection in geneticin. Production of IL-7 in these cells was induced by exposure to TT. Production of IL-4, IL-6, and interferon-gamma (IFN-gamma) was detected after antigenic stimulation; there was, however, no effect of IL-7 on the pattern or kinetics of cytokine production by these cells. Human IL-7 transduced cells showed greater proliferation to TT than control T cells, particularly at subthreshold TT concentrations. These dta imply that genetic modification of antigen-specific T cells may be a plausible strategy for the study and manipulation of the immune responses to microbial pathogens.