Lymphocyte chemoattractant factor induces CD4-dependent intracytoplasmic signaling in lymphocytes

At present, a naturally occurring soluble ligand for CD4 has not been well described. There is much evidence to indicate that MHC class II molecules can bind to CD4; however, binding of intact class II molecules under physiologic conditions has been difficult to demonstrate. We investigated whether a previously reported human lymphokine, lymphocyte chemoattractant factor (LCF), which was described for its effects on human CD4+ lymphocytes and monocytes, could associate directly with CD4 and induce the generation of second messengers. In the present study, we demonstrate that CD4 affinity-purified natural and recombinant LCF induced a rise in intracellular calcium and increased inositol trisphosphate generation in normal human CD4+ lymphocytes and murine T cell hybridomas infected to express human CD4. Cell lines lacking human CD4 or expressing human CD4 molecules that lack the intracytoplasmic domain did not demonstrate a change in either calcium or inositol trisphosphate. The effect of LCF was blocked by coincubation with either anti-CD4 antibody or Fab fragments from anti-CD4 antibody. These studies demonstrate direct interaction of a lymphokine with CD4 and generation of second messengers as a result of the interaction.