Regulation of human IgE synthesis: the role of CD4+ and CD8+ T-cells and the inhibitory effects of interferon-alpha.
Interleukin-4 (IL-4) has been shown to induce immunoglobulin E (IgE) synthesis by human peripheral blood lymphocytes (PBL). Here we show that highly purified B-cells (greater than 99.5%) failed to produce IgE in the presence of IL-4 but IgE synthesis was restored by the addition of autologous CD4+ T-cells or by CD4+ T-cell clones with non-relevant specificities, derived from different donors. In contrast, autologous CD8+ T-lymphocytes or one allogeneic CD8+ T-cell clone failed to restore IgE synthesis. Moreover, autologous CD8+ T-cells suppressed IgE synthesis induced by autologous CD4+ T-cells in a dose-dependent fashion. IgE production could be induced in cultures containing as few as 20 B-cells. Collectively these data indicate that in addition to IL-4, a second signal derived from CD4+ T-cells is required to induce B-cells to switch to IgE producing cells. In a second set of experiments we showed that IFN-alpha blocked both IL-4-induced IgE synthesis by PBL of healthy donors and spontaneous IgE synthesis by PBL of allergic or atopic patients in a dose-dependent fashion. This inhibition occurred at the IgE messenger ribonucleic acid (mRNA) transcription level. The strongest inhibitory effects of interferon-alpha (IFN-alpha) were observed at the 2.2 kb productive mRNA transcript, whereas weaker inhibitory effects were observed on the 1.7 kb germline IgE mRNA transcript.(ABSTRACT TRUNCATED AT 250 WORDS)
Gauchat
J F
JF
DNAX Research Institute, Palo Alto, CA 94304-1104.
Gascan
H
H
Roncarolo
M G
MG
Rousset
F
F
Pène
J
J
de Vries
J E
JE
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000502:physiology*; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E