TY - JOUR
T1 - Molecular regulation of human interleukin 2 and T-cell function by interleukin 4
AU - Schwarz, Edward M.
AU - Salgame, Padmini
AU - Bloom, Barry R.
PY - 1993/8/15
Y1 - 1993/8/15
N2 - Distinct functional T-cell subsets, differing in the patterns of lymphokines produced, regulate cell-mediated and humoral immune responses. The two major types and their principal products, interleukin 4 and interferon γ (IL-4 and IFN-γ), are reciprocally negatively interactive. To analyze the molecular mechanism of IL-4-mediated suppression of cell-mediated immunity we studied its effects on expression of interleukin 2 (IL-2) and IFN-γ. IL-4 pretreatment of Jurkat cells prior to stimulation resulted in a decrease in transcription of the 112 gene. IL-4 suppressed IL-2 and IFN-γ mRNA levels in primary human T cells, and addition of anti-CD28 antibodies relieved this suppression. Using enhancer-reporter constructs, IL-4 specifically down-regulated the NFIL-2B element. Electrophoretic mobility shift assays using a DNA oligomer containing the NFIL-2B binding site indicated that IL-4 inhibited the NFIL-2B complex and that the NFIL-2B DNA binding factor is distinct from AP-1. These results suggest that IL-4 may regulate development and function of T-cell subsets involved in cell-mediated immunity in part by inhibiting factors required for transcription of the IL2 gene.
AB - Distinct functional T-cell subsets, differing in the patterns of lymphokines produced, regulate cell-mediated and humoral immune responses. The two major types and their principal products, interleukin 4 and interferon γ (IL-4 and IFN-γ), are reciprocally negatively interactive. To analyze the molecular mechanism of IL-4-mediated suppression of cell-mediated immunity we studied its effects on expression of interleukin 2 (IL-2) and IFN-γ. IL-4 pretreatment of Jurkat cells prior to stimulation resulted in a decrease in transcription of the 112 gene. IL-4 suppressed IL-2 and IFN-γ mRNA levels in primary human T cells, and addition of anti-CD28 antibodies relieved this suppression. Using enhancer-reporter constructs, IL-4 specifically down-regulated the NFIL-2B element. Electrophoretic mobility shift assays using a DNA oligomer containing the NFIL-2B binding site indicated that IL-4 inhibited the NFIL-2B complex and that the NFIL-2B DNA binding factor is distinct from AP-1. These results suggest that IL-4 may regulate development and function of T-cell subsets involved in cell-mediated immunity in part by inhibiting factors required for transcription of the IL2 gene.
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M3 - Article
C2 - 8356077
SN - 0027-8424
VL - 90
SP - 7734
EP - 7738
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
ER -