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 (greater than or equal to 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 (less than or equal to 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.