SPECIFIC INTERACTION OF 4,4'-DIISOTHIOCYANATOSTILBENE-2,2'-DISULFONICACID WITH HUMAN CELLULAR CD4

We recently demonstrated that 4,4'-diisothiocyanatostilbene-2,2'-disul fonic acid (DIDS) prevented the infection of T cells by human immunode ficiency virus type-1 (Cardin et al., J. Biol. Chem. 266, 13355, 1991) . In the present study we have used a panel of monoclonal antibodies ( mabs) against a variety of human leukocyte antigens to characterize th e interaction of DIDS by flow cytometry with various T cell surface mo lecules. DIDS blocked the specific immunoreactivity of mabs OKT4A and Leu 3A with CD4 on human leukemic T cells (JM) and human mononuclear l ymphocytes with an IC50 similar to 30 mu M. The membrane distal (D1) a nd proximal (D3 and D4) domains of CD4 remained blocked for up to 5 hr of culture and returned to control levels of expression after 24 hr, reflecting the rate of membrane turnover of the CD4-DIDS complex. The binding frequencies (% positive) for anti-CD2, -CD3, -CD5, -CD6, -CD7, -CD8, -CD11a, -CD14, -CD18, -CD19, -CD45, -T cell receptor, and -HLA- DR were not significantly affected. However, there was a partial reduc tion in the antigen density of CD2, CD5, CD8, and CD11b. The selective interaction of DIDS with CD4 suggests that antagonism of the virus re ceptor may account in part for the antiviral properties of the stilben e disulfonate. (C) 1994 Academic Press, Inc.