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)
DNAX Research Institute, Palo Alto, CA 94304-1104.
J F
JF
Gauchat
H
H
Gascan
M G
MG
Roncarolo
F
F
Rousset
J
J
Pène
J E
JE
de Vries
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