CD40 ligand‐positive CD8+ T cell clones allow B cell growth and differentiation

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Abstract
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 (≥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 (⩽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.