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

JH Kim, S Ratto, KV Sitz, JD Mosca… - Human Gene …, 1994 - liebertpub.com
JH Kim, S Ratto, KV Sitz, JD Mosca, RJ McLinden, KL Tencer, MT Vahey, DS Louis, DL Birx…
Human Gene Therapy, 1994liebertpub.com
ABSTRACT 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 …
Abstract
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-γ (IFN-γ) 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 data 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.
Mary Ann Liebert