gamma/delta T lymphocytes express CD40 ligand and induce isotype switching in B lymphocytes.
T cells expressing gamma/delta T cell receptors home to epithelial tissue and may play a role in immunity to infectious agents and foreign antigens. In an effort to understand the role of gamma/delta T cells in directing B cell responses, we investigated the capacity of human gamma/delta T cells to express CD40 ligand (CD40L) and to drive immunoglobulin (Ig) isotype switching in B cells. A multiple step purification procedure resulted in the recovery of highly pure populations of peripheral blood CD4-CD8- gamma/delta T cells. Neither CD40L surface expression nor CD40L mRNA were detected in unstimulated gamma/delta T cells. Stimulation with phorbol ester and ionomycin induced CD40L mRNA and surface CD40L expression by gamma/delta T cells. Both the percentage of CD40L+ cells and the cell surface density of CD40L were significantly lower in gamma/delta T cells compared to unselected T cells. We further demonstrated that in the presence of neutralizing monoclonal antibody to interferon gamma (IFN-gamma), gamma/delta T cells could induce IgE synthesis in B cells, albeit to a lesser extent than unselected T cells. Furthermore, IgE synthesis driven by gamma/delta T cells was inhibited by monoclonal antibody to CD40L. These observations demonstrate that activated gamma/delta T cells express CD40L and can induce isotype switching in B cells.
Horner
A A
AA
Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115.
Jabara
H
H
Ramesh
N
N
Geha
R S
RS
D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D006801:Humans; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023201:CD40 Ligand; D007073:Immunoglobulin E; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate