Cytochalasin D modulates CD4 crosslinking sensitive mitogenic signal in T lymphocytes.
It has previously been shown that crosslinking of the CD4 molecule, either with anti-Leu3a mAb or with gp120 (the HIV coat protein) plus anti-gp120 mAb, suppresses activation induced by wt31, a TcR/CD3-specific mAb. This suppression was associated with hindrance of the necessary association of the p56lck kinase bearing CD4 molecule with the TcR/CD3 complex. In this paper we demonstrate that this crosslinking-induced suppression can be bypassed by perturbing the microfilament system of CD4+ cells by pretreatment with 1 microM cytochalasin D. Using the fluorescence resonance energy transfer method, we have shown that the cytochalasin D-affected increase of mitogenesis is not due to changes in the TcR/CD3 to CD4 distance. Likewise, other membrane biophysical parameters, membrane potential and lateral diffusion of surface receptors, cannot be associated with these cytochalasin D-affected mitogenic changes. Cytochalasin D treatment elevates intracellular Ca2+ levels induced by wt31 mAb plus crosslinking and generates a TcR/CD3-dependent signal which is cyclosporin sensitive.
Aszalos
A
A
Center for Drug Evaluations and Research, FDA, Washington, DC 20204.
Pine
P S
PS
Weaver
J L
JL
Rao
P E
PE
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology*; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010777:Photochemistry; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000187:drug effects / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015638:Cytochalasin D; D016572:Cyclosporine; D002118:Calcium