Positive and negative immunoregulation through CD4 depends on the concentration of the specific ligand and on the state of activation of the responding cells.
In order to better define the functional role of the interaction of CD4 polypeptide with the T-cell receptor (TCR) complex, we analysed the effect of an anti-CD4 monoclonal antibody (mAb) on T-cell activation and on the modulation of expression of CD3, CD4 and TCR variable (V) regions. The results presented here demonstrate that both positive and negative modulation of CD3 and TCR V regions can be obtained with different concentrations of the same anti-CD4 mAb and that these effects are functionally directly related to differences in IL2-receptor expression. Moreover, our data show that the dose of anti-CD4 mAb required for modulating CD3- and CD4-molecule expression on activated E+ peripheral blood mononuclear cells is at least 30 times higher than that required to obtain the same effect on resting cells. Thus, our results demonstrate that the interaction of CD4 molecule with its ligand can result in both up and downregulation of TCR and IL2-receptor expression, and that this differential modulation is strictly dependent on the concentration of available ligand as well as on the activation state of the responding cells.
Sottini
A
A
Consorzio per le Biotecnologie, Centro Nazionale delle Ricerche (CNR), Institute of Chemistry, School of Medicine, Brescia, Italy.
Albertini
A
A
Primi
D
D
Imberti
L
L
D000328:Adult; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2