Lack of p56 lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

In cell lines the endocytic properties of CD4 are regulated through its association with the src -family tyrosine kinase p56 ^lck . In lymphoid cell lines expressing p56 ^lck , CD4 is restricted to the cell surface and undergoes only limited internalization. Phosphorylation of the cytoplasmic domain of CD4 causes p56 ^lck to dissociate and activates an endocytosis signal leading to the internalization of CD4 through clathrin-coated pits. In p56 ^lck -negative transfected cell lines CD4 is constitutively internalized, but internalization is inhibited when p56 ^lck is expressed in these cells. We now demonstrate that these endocytic properties of CD4 determined in transfected cell lines hold true for CD4 naturally expressed on myeloid cell lines (HL-60 and U937), as well as on primary lymphocytes, monocytes and macrophages isolated from human blood. CD4 showed limited internalization on p56 ^lck -positive lymphocytes, but was rapidly internalized in p56 ^lck -negative monocytes and macrophages. Surprisingly, rapid internalization of CD4 was seen with the lymphocytes from one unidentified donor. In these cells we failed to detect p56 ^lck expression by Western blotting.