Induction of cognate and non-cognate T-cell help for B-cell IgE production in relation to CD40 ligand expression.
Nonactivated, fixed peripheral blood T cells (PBT) from healthy donors or patients with X-linked-hyper-IgM (HIGM) syndrome, or cloned T cells provided effective help for tonsillar B lymphocytes for induction of IgE or other immunoglobulin (Ig) isotypes. Helper activity was mediated by staphylococcal superantigens adsorbed to the T cells prior to fixation and required presence of IL-4 in the cultures. We demonstrated that the T cells neither expressed detectable CD40 ligand at the beginning of the superantigen treatment nor 24 h later. Phorbol ester (PMA) plus Ca-ionophore treatment efficiently induced CD40L. Such T cells did not, however, provide any help for B-cell activation in some experiments or stimulated only low responses in others. Antibodies against CD2, CD3 and ICAM-1 adsorbed to fixed T cells prior to coculturing inhibited helper activity. A soluble CTLA4 construct was also inhibitory. Our results suggest a pathway of B-cell activation independent of CD40L expressed on T cells.
Armerding
D
D
Sandoz Research Institute, Vienna, Austria.
Hren
A
A
Callard
R E
RE
Fu
S M
SM
Mudde
G C
GC
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000096:biosynthesis*; D000001:Calcimycin / Q000494:pharmacology; D002648:Child; D008040:Genetic Linkage; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D014066:Palatine Tonsil / Q000166:cytology; D013210:Staphylococcus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013577:Syndrome; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014960:X Chromosome / Q000276:immunology
D019013:CD40 Antigens; D007075:Immunoglobulin M; D008024:Ligands; D018089:Superantigens; D007073:Immunoglobulin E; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate