Consequences of stable transduction and antigen-inducible expression of the human interleukin-7 gene on tetanus-toxoid-specific T cells.
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.
Kim
J H
JH
Department of Retroviral Research, Walter Reed Army Institute of Research, Rockville, MD 20850.
Ratto
S
S
Sitz
K V
KV
Mosca
J D
JD
McLinden
R J
RJ
Tencer
K L
KL
Vahey
M T
MT
St Louis
D
D
Birx
D L
DL
Redfield
R R
RR
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D012190:Retroviridae / Q000235:genetics; D013745:Tetanus Toxoid / Q000276:immunology; D014161:Transduction, Genetic
D016207:Cytokines; D015851:Interleukin-7; D013745:Tetanus Toxoid