Functional analysis of the effects of a fully humanized anti-CD4 antibody on resting and activated human T cells.

A fully humanized anti-CD4 antibody was studied for its effects on resting and activated CD4 T cells. Whereas the antibody was poorly lytic, it induced dramatic down-modulation of CD4 expression on both types of cell. In order to down-modulate CD4 on resting, normal CD4 T cells there was an absolute requirement for FcR-mediated cross-linking of the anti-CD4 antibody, and only CD4 levels were affected. When activated cloned T-cell lines were studied there was no requirement for cross-linking and several other cell surface markers were also affected. Although the total cellular CD4 was reduced in the down-modulated cells, as judged by Western blot analysis, that CD4 which remained was associated with p56lck. The results are discussed in relation to the potential use of humanized anti-CD4 antibodies in the therapy of autoimmune disease and the choice of antibody isotype for such a therapeutic antibody.