Differential expression of CD40 ligand on T cell subsets - Implications for different roles of CD45RA(+) and CD45RO(+) cells in IgE production

Physical contact between human T lymphocytes and B lymphocytes is required for the induction of IgE production. In the present study, we examined the abilities of CD45RA(+) and CD45RO(+) human T cell subsets to provide help for IgE production by human peripheral blood B cells in the presence of IL-4. Purified peripheral CD45RA(+) T cells are much better inducers of IgE synthesis than are CD45RO(+) T cells. Activation of CD45RA(+) T cells, but not CD45RO(+) T cells, via the TCR/CD3 complex is sufficient to confer the ability to provide IgE help, suggesting that an inducible T cell surface molecule plays an important role in this system. The CD40 ligand, an inducible T cell surface molecule, is expressed at higher levels on CD45RA(+) T cells as compared with CD45RO(+) T cells following CD3-stimulation, Blocking of the CD40-CD40 ligand interaction in vitro by the addition of a soluble form of B cell CD40 Ag completely blocks IgE production induced by CD45RA(+) T cells. Finally, the in vitro conversion of CD45RA(+) T cells to the CD45RO(+) phenotype is accompanied by a loss in the ability of these cells to express the CD40 ligand in response to anti-CD3 stimulation as well as a loss in their ability to provide IgE help. These results suggest that both CD45 subsets may play significant and distinct roles in the induction of IgE production under physiologic conditions: CD45RO(+) T cells provide IL-4 and the CD45RA(+) subset provides the second signal via the CD40 ligand.