PMID- 1683237 OWN - NLM STAT- MEDLINE DCOM- 19911230 LR - 20181130 IS - 0904-1850 (Print) IS - 0904-1850 (Linking) VI - 13 DP - 1991 Apr TI - Regulation of human IgE synthesis: the role of CD4+ and CD8+ T-cells and the inhibitory effects of interferon-alpha. PG - 31s-38s AB - 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) FAU - Gauchat, J F AU - Gauchat JF AD - DNAX Research Institute, Palo Alto, CA 94304-1104. FAU - Gascan, H AU - Gascan H FAU - Roncarolo, M G AU - Roncarolo MG FAU - Rousset, F AU - Rousset F FAU - Pene, J AU - Pene J FAU - de Vries, J E AU - de Vries JE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur Respir J Suppl JT - The European respiratory journal. Supplement JID - 8910681 RN - 0 (Interferon alpha-2) RN - 0 (Interferon-alpha) RN - 0 (Recombinant Proteins) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - B-Lymphocytes/drug effects/*metabolism MH - CD4-Positive T-Lymphocytes/physiology MH - Clone Cells MH - Gene Expression Regulation/drug effects MH - Humans MH - Immunoglobulin E/*biosynthesis/genetics MH - Interferon alpha-2 MH - Interferon-alpha/*pharmacology MH - Interleukin-4/*physiology MH - Recombinant Proteins MH - T-Lymphocytes/*physiology MH - T-Lymphocytes, Cytotoxic/physiology MH - T-Lymphocytes, Regulatory/physiology MH - Transcription, Genetic/drug effects EDAT- 1991/04/01 00:00 MHDA- 1991/04/01 00:01 CRDT- 1991/04/01 00:00 PHST- 1991/04/01 00:00 [pubmed] PHST- 1991/04/01 00:01 [medline] PHST- 1991/04/01 00:00 [entrez] PST - ppublish SO - Eur Respir J Suppl. 1991 Apr;13:31s-38s.