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 requ ired for the induction of IgE production. In the present study, we exa mined 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 b etter inducers of IgE synthesis than are CD45RO(+) T cells. Activation of CD45RA(+) T cells, but not CD45RO(+) T cells, via the TCR/CD3 comp lex is sufficient to confer the ability to provide IgE help, suggestin g that an inducible T cell surface molecule plays an important role in this system. The CD40 ligand, an inducible T cell surface molecule, i s expressed at higher levels on CD45RA(+) T cells as compared with CD4 5RO(+) T cells following CD3-stimulation, Blocking of the CD40-CD40 li gand 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 th at both CD45 subsets may play significant and distinct roles in the in duction of IgE production under physiologic conditions: CD45RO(+) T ce lls provide IL-4 and the CD45RA(+) subset provides the second signal v ia the CD40 ligand.