The Protein Tyrosine Kinase p56lck Is Required for Triggering NF-κB Activation upon Interaction of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein gp120 with Cell Surface CD4

We have previously shown that NF-κB nuclear translocation can be observed upon human immunodeficiency virus type 1 (HIV-1) binding to cells expressing the wild-type CD4 molecule, but not in cells expressing a truncated form of CD4 that lacks the cytoplasmic domain (M. Benkirane, K.-T. Jeang, and C. Devaux, EMBO J. 13:5559–5569, 1994). This result indicated that the signaling cascade which controls HIV-1-induced NF-κB activation requires the integrity of the CD4 cytoplasmic tail and suggested the involvement of a second protein that binds to this portion of the molecule. Here we investigate the putative role of p56^lck as a possible cellular intermediate in this signal transduction pathway. Using human cervical carcinoma HeLa cells stably expressing CD4, p56^lck, or both molecules, we provide direct evidence that expression of CD4 and p56^lck is required for HIV-1-induced NF-κB translocation. Moreover, the fact that HIV-1 stimulation did not induce nuclear translocation of NF-κB in cells expressing a mutant form of CD4 at position 420 (C420A) and the wild-type p56^lck indicates the requirement for a functional CD4-p56^lck complex.     

Immune Function in Multiple Myeloma: Impaired Responsiveness to Keyhole Limpet Hemocyanin

Twenty-three patients with multiple myeloma, four patients with treated localized plasmacytoma and 14 normal subjects were immunized with keyhole limpet hemocyanin (KLH). When compared to the normal subjects, the myeloma patients showed a prolonged induction time for IgM antibody formation, a more rapid switch from IgM to IgG production and a decline in the titre of total antibody produced. In vitro lymphocyte responses to KLH following immunization were reduced in the myeloma group and tended to decline with time in a manner similar to the serum antibody concentration. Most of the myeloma patients tested developed delayed hypersensitivity skin reactions to KLH, but these reactions were smaller than those of the control subjects. The patients with myeloma had also reduced in vitro lymphocyte responses to streptolysin-O and vaccinia. Immune function of the plasmacytoma patients was similar to that of the control subjects.Both humoral and cellular immunity in response to a newly encountered antigen, KLH, is impaired in patients with multiple myeloma.