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.
Cruikshank
W W
WW
Pulmonary Center, Boston University School of Medicine, MA 02118.
Greenstein
J L
JL
Theodore
A C
AC
Center
D M
DM
D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D019410:Interleukin-16; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
D015704:CD4 Antigens; D019410:Interleukin-16; D008222:Lymphokines; D011994:Recombinant Proteins; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium