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.
Bartholomew
M
M
Biology Division, Wellcome Research Laboratories, Beckenham, Kent, UK.
Brett
S
S
Barber
K
K
Rossman
C
C
Crowe
S
S
Tite
J
J
D000920:Antibody-Dependent Cell Cytotoxicity; D015153:Blotting, Western; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology
D015704:CD4 Antigens; D007074:Immunoglobulin G; D011961:Receptors, Fc