CD40 ligand-positive CD8+ T cell clones allow B cell growth and differentiation.
A fraction of activated CD8+ T cells expresses CD40 ligand (CD40L), a molecule that plays a key role in T cell-dependent B cell stimulation. CD8+ T cell clones were examined for CD40L expression and for their capacity to allow the growth and differentiation of B cells, upon activation with immobilized anti-CD3. According to CD40L expression, CD8+ clones could be grouped into three subsets. CD8+ T cell clones expressing high levels of CD40L (> or = 80% CD40L+ cells) were equivalent to CD4+ T cell clones with regard to induction of tonsil B cell proliferation and immunoglobulin (Ig) production, provided the combination of interleukin (IL)-2 and IL-10 was added to cultures. CD8+ T cell clones, with intermediate levels of CD40L expression (10 to 30% CD40L+ cells), also stimulated B cell proliferation and Ig secretion with IL-2 and IL-10. B cell responses induced by these CD8+ T cell clones were neutralized by blocking monoclonal antibodies specific for either CD40L or CD40. By contrast, CD40L- T cell clones (< or = 5% CD40L+ cells), only induced marginal B cell responses even with IL-2 and IL-10. All three clone types were able to activate B cells as shown by up-regulation of CD25, CD80 and CD86 expression. A neutralizing anti-CD40L antibody indicated that T cell-dependent B cell activation was only partly dependent on CD40-CD40L interaction. These CD40L- clones had no inhibitory effects on B cell proliferation induced by CD40L-expressing CD8+ T cell clones. Taken together, these results indicate that CD8+ T cells can induce B cell growth and differentiation in a CD40L-CD40-dependent fashion.
Hermann
P
P
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Van-Kooten
C
C
Gaillard
C
C
Banchereau
J
J
Blanchard
D
D
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D007739:L Cells; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D014066:Palatine Tonsil / Q000166:cytology; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D018122:B7-1 Antigen; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D008934:Mitogens; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D023201:CD40 Ligand; D018819:Dipeptidyl Peptidase 4