Co-stimulation of T cells via CD28 inhibits human IgE production; reversal by pertussis toxin.
In lymphocyte cultures, IgE production was achieved by stimulating T cells with anti-CD2 and IL-2. Here we show that anti-CD28, in the presence or absence of IL-2, reduces this IgE production approximately 10-fold. This inhibition of IgE production was almost completely reversed by Pertussis toxin (PT). PT had no effect on IgE production when the cells were stimulated in the absence of anti-CD28. No major effects of PT were found on IgM production. PT had no effect on purified B cells, stimulated with IL-4 and anti-CD40. In the presence of saturating amounts of rIL-4 similar results were obtained, albeit the absolute amounts of IgE produced were higher in all situations. Furthermore, PT-induced IgE production was still dependent on IL-4, as was evident from experiments in which anti-IL-4 was added to the culture. The IgE enhancing effect was dependent on the adenosine diphosphate (ADP)-ribosyltransferase activity of PT, because a mutant molecule lacking this activity was not able to restore anti-CD28-induced inhibition of IgE synthesis. Thus, we show that co-stimulation with anti-CD28 causes an inhibition of T cell-dependent IgE production by B cells, which inhibition can be specifically overcome by PT. An analysis of the molecular pathways underlying this phenomenon may contribute to our understanding of the regulation of IgE synthesis in (patho)physiological conditions.
Van der Pouw-Kraan
C T
CT
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (CLB), Amsterdam.
Rensink
H J
HJ
Rappuoli
R
R
Aarden
L A
LA
D018106:CD28 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D037342:Pertussis Toxin; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000378:metabolism / Q000494:pharmacology*
D018106:CD28 Antigens; D007376:Interleukin-2; D010566:Virulence Factors, Bordetella; D015847:Interleukin-4; D007073:Immunoglobulin E; D011065:Poly(ADP-ribose) Polymerases; D037342:Pertussis Toxin